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Han K, Chen Y, Sun X, Wen L, Wu Y, Chen S, Wei L, Yu J, Zeng T, Jiang L, Tan L. Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer. Clin Transl Oncol 2025; 27:2005-2013. [PMID: 39397200 DOI: 10.1007/s12094-024-03722-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 09/04/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). METHODS A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. RESULTS ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CONCLUSION CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.
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Affiliation(s)
- Kexin Han
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
- School of Public Health, Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Yinyi Chen
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Xinlu Sun
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
- School of Public Health, Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Lili Wen
- Laboratory, Department of Nanchang Ninth Hospital, Nanchang, Jiangxi, People's Republic of China
| | - Yang Wu
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Simei Chen
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Liping Wei
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Jianlin Yu
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Tingting Zeng
- Department of Laboratory Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
| | - Lei Jiang
- Jiangxi Long March Hospital, Nanchang, Jiangxi, People's Republic of China
| | - Liming Tan
- Department of Laboratory Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
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Lan J, Wang H, Huang J, Li W, Ao M, Zhang W, Mu J, Yang L, Ran L. MoLPre: A Machine Learning Model to Predict Metastasis of cT1 Solid Lung Cancer. Clin Transl Sci 2025; 18:e70186. [PMID: 40143527 PMCID: PMC11947056 DOI: 10.1111/cts.70186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 12/29/2024] [Accepted: 01/10/2025] [Indexed: 03/28/2025] Open
Abstract
Given that more than 20% of patients with cT1 solid NSCLC showed nodal or extrathoracic metastasis, early detection of metastasis is crucial and urgent for improving therapeutic planning and patients' risk stratification in clinical practice. This study collected clinicopathological variables from the pulmonary nodule and lung cancer database of the First Affiliated Hospital of Chongqing Medical University, where patients with early-stage (cT1) solitary lung cancer were evaluated from 2018.11 to 2022.10. The random forest model and Shapley Additive Explanations (SHAP) were used to investigate the importance of clinical features in the feature selection part. Random Forest, Gradient Boosting, and AdaBoost classifiers were applied to build the final model, and the predictive discrimination of each model was compared based on the receiver operating characteristics (ROC) curve and precision and recall curve. With the evaluation of feature importance, 9 features were used to construct the prediction model finally. The Random Forest model yielded an average precision of 0.93 with an area under the curve (AUC) of 0.92 (95% CI: 0.88-0.94) compared with the Gradient Boosting and AdaBoost classifiers in the internal validation dataset, yielding an average precision of 0.87 and 0.91 with AUCs of 0.87 (95% CI: 0.84-0.93) and 0.90 (95% CI: 0.86-0.92), respectively. In addition, the Random Forest classifier performed best in 5 other 5 diagnostic indices. Furthermore, we embedded this model in a web application called MoLPre (https://molpre.cqmu.edu.cn/), a user-friendly tool assisting in the metastasis prediction of cT1 solid lung cancer.
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Affiliation(s)
- Jie Lan
- Department of BioinformaticsThe Basic Medical School of Chongqing Medical UniversityChongqingChina
| | - Heng Wang
- Department of BioinformaticsThe Basic Medical School of Chongqing Medical UniversityChongqingChina
| | - Jing Huang
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Weiyi Li
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Min Ao
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Wanfeng Zhang
- Department of BioinformaticsThe Basic Medical School of Chongqing Medical UniversityChongqingChina
| | - Junhao Mu
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Li Yang
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Longke Ran
- Department of BioinformaticsThe Basic Medical School of Chongqing Medical UniversityChongqingChina
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
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Yue Y, Ren Y, Lu C, Jiang N, Wang S, Fu J, Kong M, Zhang G. The research progress on meningeal metastasis in solid tumors. Discov Oncol 2025; 16:254. [PMID: 40019647 PMCID: PMC11871263 DOI: 10.1007/s12672-025-01950-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/08/2024] [Indexed: 03/01/2025] Open
Abstract
Meningeal metastasis (MM), particularly Leptomeningeal metastases (LM), represents the advanced stage of solid tumors and poses a significant threat to patients' lives. Moreover, it imposes a substantial burden on society. LM represents the ultimate and most fatal stage of solid tumors, inflicting devastating consequences on patients and imposing a substantial burden on society. The incidence of LM continues to rise annually, emphasizing the urgent need for early recognition and treatment initiation in individuals with LM to significantly extend overall patient survival. Despite rapid advancements in current LM detection and treatment methods, the diagnosis of LM remains constrained by several limitations such as low diagnostic efficiency, the therapeutic outcomes remain suboptimal. Furthermore, there is currently no universally recognized industry standard for LM treatment, further underscoring its status as an unresolved challenge in tumor management. Additionally, progress towards elucidating the mechanisms underlying MM has stagnated. Therefore, this review aims to comprehensively summarize recent research advances pertaining to MM in solid tumors by elucidating its underlying mechanisms, exploring diagnostic and prognostic biomarkers while addressing existing research challenges.
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Affiliation(s)
- Yi Yue
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Yuqing Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Chunya Lu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Nan Jiang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Sihui Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Junkai Fu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Mengrui Kong
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Guojun Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
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Wang K, Chang Z, Li Y, Wang Y, Tang Y, Gao X, Tang B. Precise detection of NSE and ProGRP with nanoprobes for early diagnosis of small cell lung cancer. Chem Commun (Camb) 2025; 61:3179-3182. [PMID: 39876812 DOI: 10.1039/d4cc06230b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
A DNA strand-based fluorescent probe was developed for the direct simultaneous detection of small cell lung cancers' tumor markers NSE and ProGRP. The probe offers stability, simplicity, and rapid response, making it highly promising for application in clinical serum samples' diagnosis.
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Affiliation(s)
- Keyi Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
| | - Zixuan Chang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
| | - Yingjie Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
| | - Yinian Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
| | - Yue Tang
- Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, 250014, P. R. China.
| | - Xiaonan Gao
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
- Laoshan Laboratory, 168Wenhai Middle Rd, Aoshanwei Jimo, Qingdao 266237, P. R. China
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Zhang Q, Pan G, Zhang L, Xu Y, Hao J. The Predictive Value of Monocarboxylate Transporter 4 (MCT4) on Lung Adenocarcinoma Patients Treated with PD-1 Inhibitors. J Inflamm Res 2024; 17:10515-10531. [PMID: 39659754 PMCID: PMC11630727 DOI: 10.2147/jir.s493632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/28/2024] [Indexed: 12/12/2024] Open
Abstract
Purpose Monocarboxylate transporter 4 (MCT4) can influence the amount of lactate in the tumor microenvironment and further control cancer cell proliferation, migration, and angiogenesis. This study aimed to evaluate the predictive value of MCT4 for prognosis and immunotherapy efficacy in advanced lung adenocarcinoma (LUAD). Patients and methods First, bioinformatics analysis was used to assess the relevance of MCT4 for survival and immunotherapy outcomes in LUAD. Subsequently, we performed a retrospective study involving 126 patients with stage IIIb to IV LUAD treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. MCT4 expression in LUAD tissues was detected by immunohistochemistry (IHC), then the patients were divided into high and low expression groups. The differences in the medical records of the two groups were compared using the X2 test. Kaplan-Meier (K-M) method was used for survival analysis. Univariate and multivariate analysis were used to pinpoint independent predictors, and a nomogram was developed based on the significant factors for overall survival (OS) in the multivariate analysis. The predictive ability of the nomogram was evaluated through C-index, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results Both bioinformatics analysis and clinical study revealed that low MCT4 expression was associated with better prognosis and immunotherapy efficacy. Multivariate analysis of clinical characteristics showed that age >65 years, stage IV, high MCT4 expression, neutrophil-to-lymphocyte ratio (NLR)>3, lactate dehydrogenase (LDH)>250 (U/L) and carcinoembryonic antigen (CEA)>5 (ng/mL) were significantly associated with poor prognosis on immunotherapy. These factors were subsequently incorporated into the nomogram model. The C-index value of the model stood at 0.735 (95% CI= 0.662 ~ 0.807), indicating robust predictive performance of the model. The DCA curve showed that the model had a notable clinical application value. Conclusion High expression of MCT4 is associated with poor prognosis and reduced efficacy of immunotherapy in patients with advanced LUAD.
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Affiliation(s)
- Qinghua Zhang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Guizhen Pan
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Lu Zhang
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Yidan Xu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Jiqing Hao
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
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Zare ME, Nasir Kansestani A, Wu X, Zhou L, Lu J, Huang J, Wang Y, Ma Y, Gao Y, Zhang J. Serum human epididymis Protein-4 outperforms conventional biomarkers in the early detection of non-small cell lung cancer. iScience 2024; 27:111211. [PMID: 39524348 PMCID: PMC11550588 DOI: 10.1016/j.isci.2024.111211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 09/25/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
We employed a three-step approach to evaluate serum immunoassay-based biomarkers for detecting non-small cell lung cancer (NSCLC). In the first step, we performed a systematic review and meta-analysis and implemented the Laboratory Medicine Best Practices (LMBP) method to identify potential biomarkers. From potential biomarkers, Carcinoembryonic antigen (CEA), cytokeratin 19-fragments (Cyfra 21-1), and human epididymis protein-4 (HE4) were categorized as LMBP "recommend." In the second step, we conducted matched-case-control validation on these recommended biomarkers and SAA, identified as the most accurate in the first step. In the third step, a re-meta-analysis was performed by integrating our experimental results and considering covariates. The final results revealed that HE4 emerged as the most reliable biomarker, offering balanced sensitivity and specificity, with accuracy unaffected by tumor stage, making it suitable for early diagnosis. Our findings support the inclusion of HE4 in clinical guidelines for NSCLC diagnosis, alongside well-established biomarkers such as Cyfra 21-1 and CEA.
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Affiliation(s)
- Mohammad Erfan Zare
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Atefeh Nasir Kansestani
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Xuanlan Wu
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Lin Zhou
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Jie Lu
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Jun Huang
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Yanzhong Wang
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Yilei Ma
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Yuzhen Gao
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
| | - Jun Zhang
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
- Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, P.R. China
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El-Sherif GHED, El-Shafy WSA, Mohammed AbdEl-Samie AA. Neuron-Specific Enolase as a Biological Marker for Welders' Pneumoconiosis. J Occup Environ Med 2024; 66:903-907. [PMID: 39118188 DOI: 10.1097/jom.0000000000003201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
OBJECTIVE The aim of the study is to investigate the relationship between serum neuron-specific enolase (NSE) and welders' pneumoconiosis, through chest x-ray and serum NSE. METHODS The exposed group included 37 welders. The nonexposed group included 38 administrative workers. Both groups underwent history taking, clinical examination, chest x-ray, serum chromium, and serum neuron-specific enolase. Air sampling was done for total suspended particles, respirable particles, and welding fumes. RESULTS All the air samples were within the national threshold limit values. Chest x-ray abnormalities were found in eight welders (21.6%), and included reticular opacities, scattered nodules or ground-glass opacities. Serum chromium and NSE were significantly higher among welders. Serum NSE correlated positively with the duration of exposure and serum chromium level among welders. CONCLUSIONS Serum NSE can be used as a biomarker for early detection of welders' pneumoconiosis.
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Liang H, Zheng Q, Lu J, Li Z, Cai T, Han H, Zhou F, Qin Z, Yao K, Ye Y. Serum cyfra21-1 is a new prognostic biomarker of penile squamous cell carcinoma. BMC Cancer 2024; 24:1240. [PMID: 39379904 PMCID: PMC11460171 DOI: 10.1186/s12885-024-13010-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 09/30/2024] [Indexed: 10/10/2024] Open
Abstract
OBJECTIVE Our study tried to evaluate the prognostic utility of preoperative serum cyfra21-1 in patients with penile squamous cell carcinoma (PSCC). METHODS This retrospective study analyzed data from 94 patients who underwent either partial or radical penectomy accompanied by bilateral inguinal or pelvic lymphadenectomy at our institution from 2010 to 2018. The median duration of follow-up was 66.5 months. Serum cyfra21-1 concentrations were quantified through enzyme-linked immunosorbent assay, with patients classified into two groups based on cyfra21-1 levels (≤ 3.30 ng/ml and > 3.30 ng/ml). The impact of cyfra21-1 levels on clinical outcomes was evaluated. RESULTS Among the 94 patients, 68 (72.3%) had normal cyfra21-1 levels, while 26 (27.6%) exhibited elevated cyfra21-1 levels. During the follow-up period, 38 patients (40.4%) experienced relapse, and 35 patients (37.2%) died from PSCC. A significantly higher occurrence of advanced pathological grades was observed in the elevated cyfra21-1 group compared to the normal group (P = 0.029). Patients with elevated cyfra21-1 levels had significantly worse disease-free survival (DFS) and disease-specific survival (DSS) than those with normal levels (P < 0.001 and P < 0.001, respectively). In multivariate analysis, cyfra21-1 (HR: 3.938, 95% CI: 1.927-8.049, P < 0.001), lymph node involvement (HR: 8.277, 95% CI: 2.261-30.298, P = 0.001), pathological grade (HR: 2.789, 95% CI: 1.110-7.010, P = 0.029), and ECOG (Eastern Cooperative Oncology Group) performance status (HR: 1.751, 95% CI: 1.028-2.983, P = 0.039) were independent predictors of worse DFS. Similarly, CYFRA 21 - 1 (HR: 3.000, 95% CI: 1.462-6.156, P = 0.003), lymph node involvement (HR: 9.174, 95% CI: 2.010-41.862, P = 0.003), and ECOG performance status (HR: 1.856, 95% CI: 1.053-3.270, P = 0.032) were independent predictors of worse DSS. CONCLUSIONS High preoperative serum cyfra21-1 levels correlate with greater tumor aggressiveness and represent a novel, effective, and convenient prognostic biomarker for PSCC.
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Affiliation(s)
- Haitao Liang
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Qiuyue Zheng
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Jiangli Lu
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Zhiyong Li
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Taonong Cai
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Hui Han
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Fangjian Zhou
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Zike Qin
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China
| | - Kai Yao
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China.
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China.
- Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
| | - Yunlin Ye
- Department of Urinary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China.
- Collaborative innovation center for Cancer Medicine, Guangzhou, 510060, P. R. China.
- Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
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Du W, Li Y, Wang X, Xie S, Ci H, Zhou J, Zhu N, Chen Z, Zheng Y, Jia H. Circular RNA circESYT2 serves as a microRNA-665 sponge to promote the progression of hepatocellular carcinoma through ENO2. Cancer Sci 2024; 115:2659-2672. [PMID: 38710213 PMCID: PMC11309938 DOI: 10.1111/cas.16207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 05/08/2024] Open
Abstract
Circular RNAs (circRNAs) have emerged as crucial regulators in tumor progression, yet their specific role in hepatocellular carcinoma (HCC) remains largely uncharacterized. In this study, we utilized high-transcriptome sequencing to identify the upregulation of circESYT2 (hsa_circ_002142) in HCC tissues. Functional experiments carried out in vivo and in vitro revealed that circESYT2 played a significant role in maintaining the growth and metastatic behaviors of HCC. Through integrative analysis, we identified enolase 2 (ENO2) as a potential target regulated by circESYT2 through the competitive endogenous RNA sponge mechanism. Additional gain- or loss-of-function experiments indicated that overexpression of circESYT2 led to a tumor-promoting effect, which could be reversed by transfection of microRNA-665 (miR-665) mimic or ENO2 knockdown in HCC cells. Furthermore, the direct interaction between miR-665 and circESYT2 and between miR-665 and ENO2 was confirmed using RNA immunoprecipitation, FISH, RNA pull-down, and dual-luciferase reporter assays, highlighting the involvement of the circESYT2/miR-665/ENO2 axis in promoting HCC progression. These findings shed light on the molecular characteristics of circESYT2 in HCC tissues and suggest its potential as a biomarker or therapeutic target for HCC treatment.
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Affiliation(s)
- Wei Du
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Ying Li
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Xufeng Wang
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Sunzhe Xie
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Hongfei Ci
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Jiaming Zhou
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Ningqi Zhu
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Zule Chen
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
| | - Yan Zheng
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic DiseaseShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Huliang Jia
- Hepatobiliary Surgery, Department of General Surgery, Huashan HospitalFudan UniversityShanghaiChina
- Cancer Metastasis InstituteFudan UniversityShanghaiChina
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10
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Zhu J, Xia H, Xu X, Zheng R, Liu C, Hong J, Huang Q. FTIR spectroscopy for assessment of hair from lung cancer patients and its application in monitoring the chemotherapy treatment effect. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 314:124185. [PMID: 38565049 DOI: 10.1016/j.saa.2024.124185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/08/2024] [Accepted: 03/22/2024] [Indexed: 04/04/2024]
Abstract
Lung cancer is the most common cancer and the leading cause of death in China. The current gold standard for clinical lung cancer diagnosis is based on histopathological examination of tumors, but it has the limitation for easy operation and convenient applications. Therefore, researchers are still striving to develop other tools and methods for non-invasive and rapid assessment of the health conditions of lung cancer patients. Hair, as a reflection of the metabolism of the body, is closely related to human health conditions. In principle, Fourier-transform infrared (FTIR) spectroscopy can probe the major chemical compositions in the hair. However, as indicated by previous studies, there is still the challenge to make good use of FTIR spectroscopy for achieving reliable analysis of hair from cancer patients. In this study, hair samples from 82 lung cancer patients were collected and subjected to FTIR measurements and analysis, which showed the protein content in the hair is closely related to the protein content in the blood serum of patients, and the contents of protein and lipid are statistically lower in the lung cancer patients. Furthermore, we demonstrated that FTIR spectroscopy could be employed to monitor the hair of lung cancer patients undergoing chemotherapy, and confirmed that the FTIR spectra of the hair may reflect the resultant effect of the chemotherapy. As such, this work validates the way of using FTIR spectroscopy in hair analysis for the assistance of medical diagnosis of lung cancer as well as monitoring the conditions of the patients under the medical treatment.
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Affiliation(s)
- Jianxia Zhu
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China; CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China
| | - Haiqian Xia
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China; CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China
| | - Xiuzhi Xu
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China
| | - Rong Zheng
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China
| | - Chao Liu
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, Anhui 230032, China
| | - Jingfang Hong
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China.
| | - Qing Huang
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China; CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China; Science Island Branch of Graduate School, University of Science and Technology of China, Hefei, Anhui 230032, China.
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11
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Galyamina AG, Kovalenko IL, Smagin DA, Kudryavtseva NN. Correlations of Expression Levels of Lung Cancer Marker Gene Eno2 and Genes of Carcinogenesis and Apoptosis in the Hypothalamus of Mice with Depression-Like Behavior. Bull Exp Biol Med 2024; 176:612-616. [PMID: 38730106 DOI: 10.1007/s10517-024-06078-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Indexed: 05/12/2024]
Abstract
We experimentally demonstrated that chronic social stress during the development of a depression-like state enhances lung metastasis and modifies the expression of many carcinogenesis- and apoptosis-related genes in the hypothalamus of mice, including genes involved in lung cancer pathogenesis in humans. Analysis of the expression of genes encoding the major clinical markers of lung cancer in the hypothalamus of mice with depression-like behavior revealed increased expression of the Eno2 gene encoding neuron-specific enolase, a blood marker of lung cancer progression in humans. It was shown that the expression of this gene in the hypothalamus correlated with the expression of many carcinogenesis- and apoptosis-related genes. The discovered phenomenon may have a fundamental significance and requires further studies.
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Affiliation(s)
- A G Galyamina
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
| | - I L Kovalenko
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
| | - D A Smagin
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
| | - N N Kudryavtseva
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
- I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia
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12
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Li L, Jiang H, Zeng B, Wang X, Bao Y, Chen C, Ma L, Yuan J. Liquid biopsy in lung cancer. Clin Chim Acta 2024; 554:117757. [PMID: 38184141 DOI: 10.1016/j.cca.2023.117757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 12/29/2023] [Accepted: 12/31/2023] [Indexed: 01/08/2024]
Abstract
Lung cancer is a highly prevalent malignancy worldwide and the primary cause of mortality. The absence of systematic and standardized diagnostic approaches for identifying potential pulmonary nodules, early-stage cancers, and indeterminate tumors has led clinicians to consider tissue biopsy and pathological sections as the preferred method for clinical diagnosis, often regarded as the gold standard. The conventional tissue biopsy is an invasive procedure that does not adequately capture the diverse characteristics and evolving nature of tumors. Recently, the concept of 'liquid biopsy' has gained considerable attention as a promising solution. Liquid biopsy is a non-invasive approach that facilitates repeated analysis, enabling real-time monitoring of tumor recurrence, metastasis, and response to treatment. Currently, liquid biopsy includes circulating tumor cells, circulating cell-free DNA, circulating tumor DNA, circulating cell-free RNA, extracellular vesicles, and other proteins and metabolites. With rapid progress in molecular technology, liquid biopsy has emerged as a highly promising and intriguing approach, yielding compelling results. This article critically examines the significant role and potential clinical implications of liquid biopsy in the diagnosis, treatment, and prognosis of lung cancer.
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Affiliation(s)
- Lan Li
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Haixia Jiang
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China
| | - Bingjie Zeng
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China
| | - Xianzhao Wang
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China
| | - Yunxia Bao
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China
| | - Changqiang Chen
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China.
| | - Lifang Ma
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China.
| | - Jin Yuan
- Department of Laboratory Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai China, Shanghai 200030, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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13
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He J, Liang G, Yu H, Lin C, Shen W. Evaluating the predictive significance of systemic immune-inflammatory index and tumor markers in lung cancer patients with bone metastases. Front Oncol 2024; 13:1338809. [PMID: 38264753 PMCID: PMC10805270 DOI: 10.3389/fonc.2023.1338809] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/13/2023] [Indexed: 01/25/2024] Open
Abstract
Objective This study aims to develop a predictive model for identifying lung cancer patients at elevated risk for bone metastases, utilizing the Unified Immunoinflammatory Index and various tumor markers. This model is expected to facilitate timely and effective therapeutic interventions, especially in the context of the growing significance of immunotherapy for lung cancer treatment. Methods A retrospective analysis was conducted on 324 lung cancer patients treated between January 2019 and January 2021. After meeting the inclusion criteria, 241 patients were selected, with 56 exhibiting bone metastases. The cohort was divided into a training group (169 patients) and a validation group (72 patients) at a 7:3 ratio. Lasso regression was employed to identify critical variables, followed by logistic regression to construct a Nomogram model for predicting bone metastases. The model's validity was ascertained through internal and external evaluations using the Concordance Index (C-index) and Receiver Operating Characteristic (ROC) curve. Results The study identified several factors influencing bone metastasis in lung cancer, such as the Systemic Immune-Inflammatory Index (SII), Carcinoembryonic Antigen (CEA), Neuron Specific Enolase (NSE), Cyfra21-1, and Neutrophil-to-Lymphocyte Ratio (NLR). These factors were incorporated into the Nomogram model, demonstrating high validation accuracy with C-index scores of 0.936 for internal and 0.924 for external validation. Conclusion The research successfully developed an intuitive and accurate Nomogram prediction model utilizing clinical indicators to predict the risk of bone metastases in lung cancer patients. This tool can be instrumental in aiding clinicians in developing personalized treatment plans, thereby optimizing patient outcomes in lung cancer care.
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Affiliation(s)
| | | | | | | | - Weiyu Shen
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
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14
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Bitter EE, Skidmore J, Allen CI, Erickson RI, Morris RM, Mortimer T, Meade A, Brog R, Phares T, Townsend M, Pickett BE, O’Neill KL. TK1 expression influences pathogenicity by cell cycle progression, cellular migration, and cellular survival in HCC 1806 breast cancer cells. PLoS One 2023; 18:e0293128. [PMID: 38033034 PMCID: PMC10688958 DOI: 10.1371/journal.pone.0293128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 10/05/2023] [Indexed: 12/02/2023] Open
Abstract
Breast cancer is the most common cancer diagnosis worldwide accounting for 1 out of every 8 cancer diagnoses. The elevated expression of Thymidine Kinase 1 (TK1) is associated with more aggressive tumor grades, including breast cancer. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement in breast cancer has not been identified. Here, we evaluate potential pathogenic effects of elevated TK1 expression by comparing HCC 1806 to HCC 1806 TK1-knockdown cancer cells (L133). Transcriptomic profiles of HCC 1806 and L133 cells showed cell cycle progression, apoptosis, and invasion as potential pathogenic pathways affected by TK1 expression. Subsequent in-vitro studies confirmed differences between HCC 1806 and L133 cells in cell cycle phase progression, cell survival, and cell migration. Expression comparison of several factors involved in these pathogenic pathways between HCC 1806 and L133 cells identified p21 and AKT3 transcripts were significantly affected by TK1 expression. Creation of a protein-protein interaction map of TK1 and the pathogenic factors we evaluated predict that the majority of factors evaluated either directly or indirectly interact with TK1. Our findings argue that TK1 elevation directly increases HCC 1806 cell pathogenicity and is likely occurring by p21- and AKT3-mediated mechanisms to promote cell cycle arrest, cellular migration, and cellular survival.
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Affiliation(s)
- Eliza E. Bitter
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Jonathan Skidmore
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Carolyn I. Allen
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Rachel I. Erickson
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Rachel M. Morris
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Toni Mortimer
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Audrey Meade
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Rachel Brog
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Tim Phares
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Michelle Townsend
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Brett E. Pickett
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Kim L. O’Neill
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
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15
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Duan X, Ouyang Z, Bao S, Yang L, Deng A, Zheng G, Zhu Y, Li G, Chu J, Liao C. Factors associated with overdiagnosis of benign pulmonary nodules as malignancy: a retrospective cohort study. BMC Pulm Med 2023; 23:454. [PMID: 37990211 PMCID: PMC10664309 DOI: 10.1186/s12890-023-02727-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 10/20/2023] [Indexed: 11/23/2023] Open
Abstract
OBJECTIVE To establish a preoperative model for the differential diagnosis of benign and malignant pulmonary nodules (PNs), and to evaluate the related factors of overdiagnosis of benign PNs at the time of imaging assessments. MATERIALS AND METHODS In this retrospective study, 357 patients (median age, 52 years; interquartile range, 46-59 years) with 407 PNs were included, who underwent surgical histopathologic evaluation between January 2020 and December 2020. Patients were divided into a training set (n = 285) and a validation set (n = 122) to develop a preoperative model to identify benign PNs. CT scan features were reviewed by two chest radiologists, and imaging findings were categorized. The overdiagnosis rate of benign PNs was calculated, and bivariate and multivariable logistic regression analyses were used to evaluate factors associated with benign PNs that were over-diagnosed as malignant PNs. RESULTS The preoperative model identified features such as the absence of part-solid and non-solid nodules, absence of spiculation, absence of vascular convergence, larger lesion size, and CYFRA21-1 positivity as features for identifying benign PNs on imaging, with a high area under the receiver operating characteristic curve of 0.88 in the validation set. The overdiagnosis rate of benign PNs was found to be 50%. Independent risk factors for overdiagnosis included diagnosis as non-solid nodules, pleural retraction, vascular convergence, and larger lesion size at imaging. CONCLUSION We developed a preoperative model for identifying benign and malignant PNs and evaluating factors that led to the overdiagnosis of benign PNs. This preoperative model and result may help clinicians and imaging physicians reduce unnecessary surgery.
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Affiliation(s)
- Xirui Duan
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China
| | - Zhiqiang Ouyang
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China
| | - Shasha Bao
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China
| | - Lu Yang
- Department of Radiology, Yunnan Cancer Hospital/Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ailin Deng
- Department of Radiology, Yunnan Cancer Hospital/Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Guangrong Zheng
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China
| | - Yu Zhu
- Department of Radiology, Yunnan Cancer Hospital/Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Guochen Li
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China
| | - Jixiang Chu
- Department of Radiology, Yunnan Cancer Hospital/Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Chengde Liao
- Department of Radiology, Yan'an Hospital of Kunming City (Yan'an Hospital Affiliated to Kunming Medical University; Yunnan Cardiovascular Hospital), Kunming, China.
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16
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Ren L, Yang Y. Value of dual-source CT dual-energy parameters combined with serum detection of VEGF and CEA in the diagnosis of early lung cancer. Biotechnol Genet Eng Rev 2023; 39:1000-1011. [PMID: 36658729 DOI: 10.1080/02648725.2023.2166708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/05/2023] [Indexed: 01/21/2023]
Abstract
To discuss the value of dual-source CT dual-energy parameters combined with serum detection of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in the diagnosis of early lung cancer (LC). In total, 100 patients with lung lesions in our hospital from January 2020 to January 2022 were selected for retrospective study, and were divided into the lung cancer group (group A) and benign lung disease group (group B) according to the final results of pathological diagnosis, using dual-source CT dual-energy scanning combined with serum detection of VEGF and CEA to analyze the diagnostic values of single detection and combined detection. Among the 100 patients with lung lesions, there were 58 patients with LC and 42 patients with benign lung diseases after pathological examination, with no statistical difference in normalized iodine concentration (NIC) and the increased value of iodine at arterial phase between the two groups (P > 0.05). The NIC value of group A was higher than group B at venous phase (P < 0.05). The serum levels of VEGF and CEA in group A were higher than group B (P < 0.05). The area under the curve, specificity, sensitivity, Youden index and 95% CI of combined diagnosis were higher than single detection of NIC, VEGF and CEA at venous phase. The combined application of dual-source CT dual-energy parameters and serum detection of VEGF and CEA has higher diagnostic value in patients with early LC, which can provide effective reference for clinical diagnosis and treatment, with higher application value in clinic.
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Affiliation(s)
- Liliang Ren
- Imaging Department, Yantai Mountain Hospital, Yantai, Shandong, China
| | - Yulong Yang
- Department of Respiratory and Critical Care Medicine, Hebei Yanda Hospital, Langfang, Hebei, China
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17
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Wu M, Ye M. Transcription factor Dp-1 knockdown downregulates thymidine kinase 1 expression to protect against proliferation and epithelial-mesenchymal transition in cervical cancer. Funct Integr Genomics 2023; 23:301. [PMID: 37715794 DOI: 10.1007/s10142-023-01218-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/08/2023] [Accepted: 08/21/2023] [Indexed: 09/18/2023]
Abstract
Thymidine kinase 1 (TK1) level is an independent survival prognostic factor for both premalignant and malignant cervical pathologies. Herein, this study sought to probe the impacts of TK1 on cervical cancer (CC) progression and its underlying mechanism. Transcription factor Dp-1 (TFDP1) and TK1 expression was assessed using qRT-PCR in CC cell lines. After ectopic expression and knockdown experiments, cell counting kit-8 and colony formation assays were adopted to measure cell proliferation, western blot to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins, and Transwell assays to assess cell invasion and migration. The binding of TFDP1 to TK1 was predicted by bioinformatic sites and verified by chromatin immunoprecipitation and dual-luciferase reporter assays. Tumor xenograft experiments in nude mice were performed to validate the influence of TFDP1/TK1 on CC progression in vivo. CC cells had high TK1 and TFDP1 expression. TFDP1 or TK1 knockdown restrained CC cell EMT, invasion, migration, and proliferation. TFDP1 facilitated TK1 expression in CC via transcription. Overexpression of TK1 counteracted the suppressive impacts of TFDP1 knockdown on CC cell malignant behaviors. Moreover, TFDP1 knockdown depressed CC growth in vivo by downregulating TK1. TFDP1 knockdown restricted proliferation and EMT in CC by downregulating TK1 expression.
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Affiliation(s)
- Mei Wu
- Department of Gynecologic Oncology, Hunan Cancer Hospital, Changsha, Hunan, 410013, People's Republic of China
| | - Mingji Ye
- Department of Urology Surgery, Hunan Cancer Hospital, No. 283, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, People's Republic of China.
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18
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Wang D, Li P, Fei X, Che S, Li J, Xuan Y, Wang J, Han Y, Gu W, Wang Y. A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules. J Gene Med 2023; 25:e3529. [PMID: 37194408 DOI: 10.1002/jgm.3529] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/20/2023] [Accepted: 05/01/2023] [Indexed: 05/18/2023] Open
Abstract
BACKGROUND Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.
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Affiliation(s)
- Dong Wang
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Peng Li
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiang Fei
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shuyu Che
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jinlong Li
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yunpeng Xuan
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jinglong Wang
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yudong Han
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Weiqing Gu
- Department of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, China
| | - Yongjie Wang
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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Fu L, Mu Z, Zhou J, Qing M, Bai L. "Gold-plated" PCN-222(Fe) and superconductive carbon black-based sandwich-type immunosensor for detecting CYFRA21-1. J Mater Chem B 2023; 11:8262-8270. [PMID: 37578169 DOI: 10.1039/d3tb01245j] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment dissolved in the blood after apoptosis of lung epithelial cells, which is a predictive biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Detection of serum CYFRA21-1 has a significant clinical value in diagnosis, monitoring and prognosis of NSCLC. Herein, a novel electrochemical immunosensor was constructed for the sensitive detection of CYFRA21-1. First, superconductive carbon black (KB) functionalized polyethyleneimine (PEI)-gold nanoparticles (AuNPs) were covered on the surface of methylene blue (MB) and used as substrate materials to immobilize the CYFRA21-1 antibody. Then, target CYFRA21-1 was successfully detected using an electrochemical immunosensor through specific recognition of antigen and antibody. The zirconium-based metal organic framework of PCN-222(Fe) with a large pore size and three-dimensional (3D) structure can absorb abundant AuNPs through strong electrostatic interaction, which enhances the conductive properties of PCN-222(Fe) and prevents the self-aggregation of AuNPs. However, PCN-222(Fe) with peroxidase-like activity can catalyze the generation of hydroxyl free radicals (˙OH) from H2O2, which oxidized MB, leading to a decrease in the current signal. The signal response to the degradation of MB was recorded using differential pulse voltammetry (DPV). This indirect method of immunosensor offered a new strategy to address the limitations imposed by the poor conductivity of PCN-222(Fe), further enabling the amplification of the signal through the oxidative degradation of MB. Compared with traditional electrochemical immunosensors, this method has the advantages of a stable current signal and good reproducibility, providing a promising reference for the broad application of PCN-222(Fe) in electrochemical biosensors.
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Affiliation(s)
- Lin Fu
- Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P. R. China.
| | - Zhaode Mu
- Research Center for Pharmacodynamic Evaluation Engineering Technology of Chongqing, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P. R. China.
| | - Jing Zhou
- Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P. R. China.
| | - Min Qing
- Research Center for Pharmacodynamic Evaluation Engineering Technology of Chongqing, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P. R. China.
| | - Lijuan Bai
- Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P. R. China.
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Ke S, Chen S, Jiang Y, Gong H, Yu J, Li X, Chen Y, Li X, Wang Q, Liu Y. Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022. CANCER INNOVATION 2023; 2:265-282. [PMID: 38089746 PMCID: PMC10686150 DOI: 10.1002/cai2.74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 03/15/2023] [Accepted: 04/04/2023] [Indexed: 10/15/2024]
Abstract
Background Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.
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Affiliation(s)
- Shi‐Peng Ke
- The Second Clinical Medical SchoolNanchang UniversityNanchangChina
| | - Si‐Mei Chen
- Department of Blood TransfusionThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
| | - Yi Jiang
- The Ophthalmology & Optometry SchoolNanchang UniversityNanchangChina
| | | | - Jia‐Li Yu
- The Second Clinical Medical SchoolNanchang UniversityNanchangChina
| | - Xu Li
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
- School of Public HealthNanchang UniversityNanchangChina
| | - Yin‐Yi Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
- School of Public HealthNanchang UniversityNanchangChina
| | - Xiao‐Hang Li
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
- School of Public HealthNanchang UniversityNanchangChina
| | - Qun‐Xia Wang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
- School of Public HealthNanchang UniversityNanchangChina
| | - Yan‐Zhao Liu
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang UniversityJiangxi Province Key Laboratory MedicineNanchangChina
- School of Public HealthNanchang UniversityNanchangChina
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Pan J, Liu H, Li S, Wei W, Mai J, Bian Y, Ning S, Li J, Zhang L. The critical role of serum thymidine kinase 1(STK1) in predicting prognosis for immunotherapy in T4 stage lung squamous cell carcinoma. Heliyon 2023; 9:e14129. [PMID: 36938402 PMCID: PMC10018465 DOI: 10.1016/j.heliyon.2023.e14129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/22/2023] [Accepted: 02/22/2023] [Indexed: 03/02/2023] Open
Abstract
Purpose The role of serum thymidine kinase 1 (STK1) in predicting the prognosis of T4-stage lung squamous cell carcinoma (LUSC) with immunotherapy is the focus of our work. Methods A total of 180 LUSC patients were enrolled. In this study, according to the T stage, the patients were divided into two groups: the T1-T2 stage and the T3-T4 stage. Receiver operating characteristic (ROC) curves were used to determine the best cutoff value for predicting overall survival (OS) outcomes. The next step is to use this cutoff value to introduce univariate and multivariate Cox regression models to screen the prognostic factors in different T stages of LUSC. The association of STK1 with other clinicopathological factors was also determined. Finally, to further explore the link between STK1 and the staging of LUSC patients, we have further divided the staging into T1-3 and T4 stages. We identified factors influencing the prognosis of patients who received immunotherapy in T4 stage LUSC. Results First, we determined that the optimal cutoff for STK1 for predicting OS outcome was 1.165 pmol/L. Correlation analysis revealed that STK1 was over-expressed in LUSC patients at the T3-4 stage. Univariate and multivariate analysis showed that immunotherapy was an independent prognostic factor in patients with T4 stage LUSC. In the group of patients who received immunotherapy or not, the STK1 expression level was found to be an independent prognostic factor in T4 LUSC patients receiving PD-1/PD-L1 inhibitor treatment; patients with high levels of STK1 had an increased risk of death (95%CI = 1.028-2.04). Conclusion STK1 is associated with a higher T stage and may be an effective prognostic marker for advanced LUSC immunotherapy patients.
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Affiliation(s)
- Jinmiao Pan
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Haizhou Liu
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shirong Li
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wene Wei
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jinling Mai
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yingzhen Bian
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shufang Ning
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jilin Li
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Corresponding author. Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Litu Zhang
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Corresponding author. Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Wang T, Yue Y, Fan Z, Jia Z, Yu X, Liu C, Hou Y. Spectral Dual-Layer Computed Tomography Can Predict the Invasiveness of Ground-Glass Nodules: A Diagnostic Model Combined with Thymidine Kinase-1. J Clin Med 2023; 12:jcm12031107. [PMID: 36769756 PMCID: PMC9917490 DOI: 10.3390/jcm12031107] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aimed to evaluate the quantitative and qualitative parameters generated from SDCT for predicting the pathological subtypes of GGN-featured lung adenocarcinoma combined with TK1 and TAP. MATERIAL AND METHODS Between July 2021 and September 2022, 238 patients with GGNs were retrospectively enrolled in this study. SDCT and tests for TK1 and TAP were performed preoperatively, and the lesions were divided into glandular precursor lesions (PGL), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC), according to the pathological results. A receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of these parameters. Multivariate logistic regression analysis was performed to construct a joint diagnostic model and create a nomogram. RESULTS This study included 238 GGNs, including 41 atypical adenomatous hyperplasias (AAH), 62 adenocarcinomas in situ (AIS), 49 MIA, and 86 IAC, with a high proportion of women, non-smokers, and pure ground-glass nodule (pGGN). CT100 keV (a/v), electronic density (EDW) (a/v), Daverage, Dsolid, TK1, and TAP of MIA and IAC were higher than those of PGL. The effective atomic number (Zeff (a/v)) was lower in MIA and IAC than in PGL (all p < 0.05). Logistic regression analysis showed that Zeff (a), EDW (a), TK1, Daverage, and internal bronchial morphology were crucial factors in predicting the aggressiveness of GGN. Zeff (a) had the highest diagnostic performance with an area under the ROC curve (AUC) = 0.896, followed by EDW (a) (AUC = 0.838) and CT100 keVa (AUC = 0.819). The diagnostic model and nomogram constructed using these five parameters (Zeff (a) + EDW (a) + CT100 keVa + Daverage + TK1) had an AUC = 0.933, which was higher than the individual parameters (p < 0.05). CONCLUSIONS Multiple quantitative and functional parameters can be selected based on SDCT, especially Zeff (a) and EDW (a), which have high sensitivity and specificity for predicting GGNs' invasiveness. Additionally, the combination of TK1 can further improve diagnostic performance, and using a nomogram is helpful for individualized predictions.
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Affiliation(s)
- Tong Wang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yong Yue
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Zheng Fan
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Zheng Jia
- Philips (China) Investment Co., Ltd., Shanghai 200072, China
| | - Xiuze Yu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Chen Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yang Hou
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Correspondence: ; Tel.: +86-96615-73218
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Zhou Q, He Q, Peng L, Huang Y, Li K, Liu K, Li D, Zhao J, Sun K, Li A, He W. Preoperative diagnosis of solitary pulmonary nodules with a novel hematological index model based on circulating tumor cells. Front Oncol 2023; 13:1150539. [PMID: 37207165 PMCID: PMC10189144 DOI: 10.3389/fonc.2023.1150539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/19/2023] [Indexed: 05/21/2023] Open
Abstract
Objective Preoperative noninvasive diagnosis of the benign or malignant solitary pulmonary nodule (SPN) is still important and difficult for clinical decisions and treatment. This study aimed to assist in the preoperative diagnosis of benign or malignant SPN using blood biomarkers. Methods A total of 286 patients were recruited for this study. The serum FR+CTC, TK1, TP, TPS, ALB, Pre-ALB, ProGRP, CYFRA21-1, NSE, CA50, CA199, and CA242 were detected and analyzed. Results In the univariate analysis, age, FR+CTC, TK1, CA50, CA19.9, CA242, ProGRP, NSE, CYFRA21-1, and TPS showed the statistical significance of a correlation with malignant SPNs (P <0.05). The highest performing biomarker is FR+CTC (odd ratio [OR], 4.47; 95% CI: 2.57-7.89; P <0.001). The multivariate analysis identified that age (OR, 2.69; 95% CI: 1.34-5.59, P = 0.006), FR+CTC (OR, 6.26; 95% CI: 3.09-13.37, P <0.001), TK1 (OR, 4.82; 95% CI: 2.4-10.27, P <0.001), and NSE (OR, 2.06; 95% CI: 1.07-4.06, P = 0.033) are independent predictors. A prediction model based on age, FR+CTC, TK1, CA50, CA242, ProGRP, NSE, and TPS was developed and presented as a nomogram, with a sensitivity of 71.1% and a specificity of 81.3%, and the AUC was 0.826 (95% CI: 0.768-0.884). Conclusions The novel prediction model based on FR+CTC showed much stronger performance than any single biomarker, and it can assist in predicting benign or malignant SPNs.
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Affiliation(s)
- Qiuxi Zhou
- Department of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Qiao He
- Department of Clinical Laboratory, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Ling Peng
- Department of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Yecai Huang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Kexun Li
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Kun Liu
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Da Li
- Department of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Jing Zhao
- Department of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
| | - Kairong Sun
- Department of Respiratory Medicine, Sichuan Academy Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, China
| | - Aoshuang Li
- Department of Gastroenterology, Chengdu Third People’s Hospital, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Wenwu He
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China
- *Correspondence: Wenwu He,
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Huang H, Yang Y, Zhu Y, Chen H, Yang Y, Zhang L, Li W. Blood protein biomarkers in lung cancer. Cancer Lett 2022; 551:215886. [PMID: 35995139 DOI: 10.1016/j.canlet.2022.215886] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/12/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022]
Abstract
Lung cancer has consistently ranked first as the cause of cancer-associated mortality. The 5-year survival rate has risen slowly, and the main obstacle to improving the prognosis of patients has been that lung cancer is usually diagnosed at an advanced or incurable stage. Thus, early detection and timely intervention are the most effective ways to reduce lung cancer mortality. Tumor-specific molecules and cellular elements are abundant in circulation, providing real-time information in a noninvasive and cost-effective manner during lung cancer development. These circulating biomarkers are emerging as promising tools for early detection of lung cancer and can be used to supplement computed tomography screening, as well as for prognosis prediction and treatment response monitoring. Serum and plasma are the main sources of circulating biomarkers, and protein biomarkers have been most extensively studied. In this review, we summarize the research progress on three most common types of blood protein biomarkers (tumor-associated antigens, autoantibodies, and exosomal proteins) in lung cancer. This review will potentially guide researchers toward a more comprehensive understanding of candidate lung cancer protein biomarkers in the blood to facilitate their translation to the clinic.
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Affiliation(s)
- Hong Huang
- Institute of Clinical Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China; Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Yongfeng Yang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Yihan Zhu
- Institute of Clinical Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Hongyu Chen
- Institute of Clinical Pathology, Key Laboratory of Transplantation Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Ying Yang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Li Zhang
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Weimin Li
- Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, 610041, China.
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Jiang C, Zhao M, Hou S, Hu X, Huang J, Wang H, Ren C, Pan X, Zhang T, Wu S, Zhang S, Sun B. The Indicative Value of Serum Tumor Markers for Metastasis and Stage of Non-Small Cell Lung Cancer. Cancers (Basel) 2022; 14:5064. [PMID: 36291848 PMCID: PMC9599954 DOI: 10.3390/cancers14205064] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/11/2022] [Accepted: 10/13/2022] [Indexed: 11/18/2022] Open
Abstract
Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients.
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Affiliation(s)
- Chunyang Jiang
- Department of Thoracic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China
- Department of Thoracic Surgery, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
- Department of Thoracic Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Mengyao Zhao
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shaohui Hou
- Department of Thoracic Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Xiaoli Hu
- Department of Respiratory, The Second People’s Hospital of Linhai City, Linhai 317000, China
| | - Jinchao Huang
- Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300181, China
| | - Hongci Wang
- Baodi District People’s Hospital of Tianjin, Tianjin Baodi Hospital of Tianjin Medical University, Tianjin 301000, China
| | - Changhao Ren
- Medical College, Nankai University, Tianjin 300071, China
| | - Xiaoying Pan
- Medical College, Nankai University, Tianjin 300071, China
| | - Ti Zhang
- Medical College, Nankai University, Tianjin 300071, China
| | - Shengnan Wu
- Medical College, Nankai University, Tianjin 300071, China
| | - Shun Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Bingsheng Sun
- Department of Thoracic Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300181, China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300181, China
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Zhu H, Zheng C, Liu H, Kong F, Kong S, Chen F, Tian Y. Significance of macrophage infiltration in the prognosis of lung adenocarcinoma patients evaluated by scRNA and bulkRNA analysis. Front Immunol 2022; 13:1028440. [PMID: 36311801 PMCID: PMC9597471 DOI: 10.3389/fimmu.2022.1028440] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose To investigate the significance of macrophage infiltration to the prognosis of lung adenocarcinoma. Methods R language bioinformatics analysis technology, was used to obtain macrophage infiltration-related module genes through WGCNA (Weighted Gene Co-Expression Network Analysis). Marker genes of macrophage subtypes were identified using single-cell sequencing of lung adenocarcinoma tissue. Risk score models were constructed and validated using external data cohorts and clinical samples. Results Analysis of cohorts TCGA-LUAD, GSE11969, GSE31210, GSE50081, GSE72094 and GSE8894, revealed a negative correlation between macrophage infiltration and survival. Immunohistochemical analyses of clinical samples were consistent with these data. Based on cell-cluster-markers and TAMs-related-genes, TOP8 genes were obtained (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, and TK1) with a significant association to prognosis. Risk score models including 9 factors (C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65) for prognosis were constructed. The efficacy, stability and generalizability of the risk score models were validated using multiple data cohorts (GSE19188, GSE26939, GSE31210, GSE50081, GSE42127, and GSE72094). Conclusions Macrophage infiltration negatively correlates with prognosis in patients with lung adenocarcinoma. Based on cell-cluster-markers and TAMs-related-genes, both TOP8 genes (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, TK1) and risk score models using C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65 could predict disease prognosis.
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Affiliation(s)
- Huaiyang Zhu
- Department of Thoracic Surgery, Shandong Second Provincial General Hospital, Jinan, China
| | - Chunning Zheng
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China
| | - Hongtao Liu
- Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pathology, Shandong Lung Cancer Institute, Shandong Institute of Nephrology, Jinan, China
| | - Fanhua Kong
- Department of Thoracic Surgery, The Affiliated Taian City Centeral Hospital of Qingdao University, Taian, China
| | - Shuai Kong
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China
| | - Feng Chen
- Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yuan Tian
- Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China
- Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, China
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Zhu Y, Cui Y, Zheng X, Zhao Y, Sun G. Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166557. [PMID: 36162624 DOI: 10.1016/j.bbadis.2022.166557] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 08/27/2022] [Accepted: 09/19/2022] [Indexed: 11/30/2022]
Abstract
Lung cancer is the most malignant human cancer worldwide, also with the highest incidence rate. However, small-cell lung cancer (SCLC) accounts for 14 % of all lung cancer cases. Approximately 10 % of patients with SCLC have brain metastasis at the time of diagnosis, which is the leading cause of death of patients with SCLC worldwide. The median overall survival is only 4.9 months, and a long-tern cure exists for patients with SCLC brain metastasis due to limited common therapeutic options. Recent studies have enhanced our understanding of the molecular mechanisms leading to meningeal metastasis, and multimodality treatments have brought new hopes for a better cure for the disease. This review aimed to offer an insight into the cellular processes of different metastatic stages of SCLC revealed by the established animal models, and into the major diagnostic methods of SCLC. Additionally, it provided in-depth information on the recent advances in SCLC treatments, and highlighted several new models and biomarkers with promises to improve the prognosis of SCLC.
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Affiliation(s)
- Yingze Zhu
- Department of Hebei Key Laboratory of Medical-industrial Integration Precision Medicine, School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China
| | - Yishuang Cui
- Department of Hebei Key Laboratory of Medical-industrial Integration Precision Medicine, School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China
| | - Xuan Zheng
- Department of Hebei Key Laboratory of Medical-industrial Integration Precision Medicine, School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China
| | - Yue Zhao
- Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
| | - Guogui Sun
- Department of Hebei Key Laboratory of Medical-industrial Integration Precision Medicine, School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China.
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28
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Sun Z, Li P, Wu Z, Li B, Li W, Zhao M, Zhou X, Wang Z, Yu Z, Liu W, Zhu W, Wang H, Wang Y. Circulating CD45+EpCAM+ cells as a diagnostic marker for early-stage primary lung cancer. FRONTIERS IN MEDICAL TECHNOLOGY 2022; 4:982308. [PMID: 36147748 PMCID: PMC9487715 DOI: 10.3389/fmedt.2022.982308] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
Lung cancer is a highly prevalent type of cancer, accounting for 11.6% of all cancer incidences. Early detection and treatment can significantly improve the survival rate and quality of life of patients; however, there is no accurate, effective, and easy-to-use test for early lung cancer screening. In this study, flow cytometry was used to detect the presence of CD45+EpCAM+ cells in tumor tissues and peripheral blood mononuclear cells (PBMCs) in patients with lung cancer. Moreover, the proportion of CD45+EpCAM+ cells in PBMCs of patients with lung cancer was found to be significantly higher than that of healthy volunteers. Tumor-related serum markers level was also measured in the peripheral blood of these patients using an electrochemiluminescence assay. The correlation between CD45+EpCAM+ cells, carcinoembryonic antigen (CEA), and lung cancer was investigated using receiver operating characteristic (ROC) curve analysis, which showed the sensitivity and specificity of the CD45+EpCAM+ cell to be 81.58% and 88.89%, respectively. Further analysis yielded an area under the ROC curve (ROC/area under the curve [AUC]) of 0.845 in patients PBMCs with lung cancer, which was slightly higher than that of CEA (0.732). Therefore, the detection of CD45+EpCAM+ cells in PBMCs may be helpful for the early screening and auxiliary diagnosis of lung cancer.
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Affiliation(s)
- Zhen Sun
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Peng Li
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhaojun Wu
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Bin Li
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Wenjing Li
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | | | - Xiaobin Zhou
- Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, China
| | - Zeyao Wang
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Zhongjie Yu
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Wenna Liu
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Wenshu Zhu
- Qingdao Sino-Cell Biomed Co., Ltd., Qingdao, China
| | - Haibo Wang
- Institute of Translational Research for Solid Tumor, Qingdao University, Qingdao, China
- *Correspondence: Haibo Wang
| | - Yongjie Wang
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- Yongjie Wang
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Prognosis value of IL-6, IL-8, and IL-1β in serum of patients with lung cancer: A fresh look at interleukins as a biomarker. Heliyon 2022; 8:e09953. [PMID: 35928100 PMCID: PMC9343932 DOI: 10.1016/j.heliyon.2022.e09953] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/07/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
Interleukins are assumed to be closely related to the occurrence and development of human malignant tumors, while a few of them were commonly used as diagnostic markers in clinical cancer, including lung cancer. This study aimed to explore the value of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) combined with carcinoembryonic antigen (CEA) as biomarker panel for the diagnosis and metastasis prediction of lung cancer. IL-1β, IL-6, IL-8, and CEA in serum were determined using electrochemiluminescence immunoassay (ECLIA) and flow cytometry, and the diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic fitting regression. We found that the levels of serum IL-1β, IL-6, and IL-8 showed no significant difference among squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, while they were significantly higher in the lung cancer group or benign group than those in the healthy group. The levels of IL-8 and CEA were positively correlated with clinical stages respectively. Importantly, the panel of CEA + IL-6 + IL-8 has the highest efficacy for the diagnosis of lung cancer (AUC = 0.883) among all the detected panels, while the panel of IL-8 + CEA showed the most promising predictive value for the lymph node metastasis (AUC = 0.686) and distant metastasis of lung cancer (AUC = 0.793). In conclusion, IL-6 and IL-8 could be used as promising molecular biomarkers to diagnose and predict the metastasis of lung cancer independent of pathological types, improving the specificity and sensitivity of diagnosis for lung cancer when they were combined with CEA.
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Yuan J, Sun Y, Wang K, Wang Z, Li D, Fan M, Bu X, Chen J, Wu Z, Geng H, Wu J, Xu Y, Chen M, Ren H. Development and validation of reassigned CEA, CYFRA21-1 and NSE-based models for lung cancer diagnosis and prognosis prediction. BMC Cancer 2022; 22:686. [PMID: 35729538 PMCID: PMC9214980 DOI: 10.1186/s12885-022-09728-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 05/23/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The majority of lung cancer(LC) patients are diagnosed at advanced stage with a poor prognosis. However, there is still no ideal diagnostic and prognostic prediction model for lung cancer. METHODS Data of CEA, CYFRA21-1 and NSE test of patients with LC and benign lung diseases (BLDs) or healthy people from Physical Examination Center was collected. Samples were divided into three data sets as needed. Reassign three kinds of tumor markers (TMs) according to their distribution characteristics in different populations. Diagnostic and prognostic models were thus established, and independent validation was conducted with other data sets. RESULTS The diagnostic prediction model showed good discrimination ability: the area under the receiver operating characteristic curve (AUC) differentiated LC from healthy people and BLDs (diagnosed within 2 months), being 0.88 and 0.84 respectively. Meanwhile, the prognostic prediction model did great in prediction: AUC in training data set and test data set were 0.85 and 0.8 respectively. CONCLUSION Reassigned CEA, CYFRA21-1 and NSE can effectively predict the diagnosis and prognosis of LC. Compared with the same TMs that were considered individually, this diagnostic prediction model can identify high-risk population for LC screening more accurately. The prognostic prediction model could be helpful in making more scientific treatment and follow-up plans for patients.
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Affiliation(s)
- Jingmin Yuan
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China.,Health Science Center, Yangtze University, Jingzhou, China
| | - Yan Sun
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Ke Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Zhiyi Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Duo Li
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Meng Fan
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Xiang Bu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China
| | - Jun Chen
- Shaanxi Health Information Center, Xi'an, China
| | - Zhiquan Wu
- Medical Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hui Geng
- Physical Examination Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiamei Wu
- Shaanxi Huizhong Kangyun Medical Information Co., Ltd., Xi'an, China
| | - Ying Xu
- Office of Medical Information Management, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mingwei Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China. .,Shaanxi Provincial Research Center for the Project of Prevention and Treatment of Respiratory Diseases, Xi'an, China.
| | - Hui Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province, China. .,Shaanxi Provincial Research Center for the Project of Prevention and Treatment of Respiratory Diseases, Xi'an, China. .,Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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31
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Wang L, Lei X, Wang X. Efficacy and Safety of PD-1/PD-L1 Inhibitor Chemotherapy Combined with Lung Cancer Fang No. 1 in Relapsed and Refractory SCLC: A Retrospective Observational Study. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:2848220. [PMID: 35586668 PMCID: PMC9110176 DOI: 10.1155/2022/2848220] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/22/2022] [Accepted: 04/01/2022] [Indexed: 11/25/2022]
Abstract
Background Relapsed and refractory small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of patients is poor. The 5-year survival rate is almost 0. The average survival time of patients who refuse to receive treatment is only 2-4 months. For patients with extensive-stage SCLC, the current first-line treatment regimens are mainly platinum-containing double-drug chemotherapy. Poside combined with cisplatin/carboplatin and irinotecan combined with cisplatin/carboplatin are commonly used clinical regimens for the treatment of patients with extensive-stage SCLC. Although SCLC is very sensitive to radiotherapy and chemotherapy, most patients will develop recurrence and metastasis after initial treatment. Therefore, it is necessary to study clinically effective therapeutic drugs for relapsed and refractory SCLC. Objective To investigate the relationship between programmed death receptor-1 (programmed death receptor-1 (PD-1)) and programmed death receptor-ligand 1 (programmed death-ligand 1 (PD-L1)) inhibitors and Lung Cancer No. 1 efficacy and safety of Lung Cancer Fang No. 1 in the treatment of relapsed and refractory SCLC. Methods 80 patients with refractory SCLC were selected and randomly divided into control group and treatment group with 40 cases in each group. Among them, the control group received PD-1/PD-L1 inhibitor chemotherapy, and the treatment group received PD-1/PD-L1 inhibitor chemotherapy combined with Lung Cancer Fang No. 1 treatment. The differences in immune and tumor marker levels, clinical efficacy, and prognostic complications between the two groups before and after treatment were observed and compared. Results Before treatment, there was no significant difference in clinical improvement between the two groups. After treatment, the clinical symptom scores and body weight changes in the treatment group were significantly improved. The clinical symptom scores in the treatment group were lower than those in the control group, but the body weight changes were higher than those in the control group. The difference was statistically significant (P < 0.05). Before treatment, there was no significant difference in the levels of tumor markers between the two groups. After treatment, the levels of CYFRA21-1, CA125, and VGEF in the treatment group were significantly lower than those in the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in the immune level between the two groups before treatment (P > 0.05), while the differences in CD4+, CD3+, and CD4+/CD8+ after treatment were significant, and the treatment group was higher than the control group, with statistical significance (P < 0.05). After treatment, the clinical efficacy of the two groups was significantly improved. The DCR90.00% of the treatment group was significantly higher than that of the control group, 67.50%, and the difference was statistically significant (P < 0.05). The analysis of complications after treatment showed that fatigue, anorexia, hypertension, hand-foot syndrome, diarrhea, leukopenia, thrombocytopenia, and urinary protein in the treatment group were significantly lower than those in the control group, and the difference was statistically significant (P < 0.05). Conclusion PD-1/PD-L1 inhibitor chemotherapy combined with Lung Cancer Fang No. 1 has a good and safe effect on SCLC patients. It has a good curative effect in improving the clinical symptoms of patients. It can stabilize the tumor, inhibit the development of lung cancer, improve the body's cellular immune function, adjust the level and expression of tumor markers, improve the body's material metabolism, and restore the balance of yin and yang in the body.
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Affiliation(s)
- Lihua Wang
- Department of Respiratory Endology, People's Hospital of Dongxihu District, Wuhan, Hubei 430040, China
| | - Xiaoxia Lei
- Second Ward, Department of Respiratory and Critical Care Medicine, Wuhan No. 1 Hospital, China
| | - Xin Wang
- Department of Infectious Disease, Wuhan Asia General Hospital, China
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Min L, Zhu T, Lv B, An T, Zhang Q, Shang Y, Yu Z, Zheng L, Wang Q. Exosomal LncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer. Int J Clin Oncol 2022; 27:1013-1024. [PMID: 35482171 PMCID: PMC9120093 DOI: 10.1007/s10147-022-02129-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 01/24/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. For lack of conveniently sensitive and specific biomarkers, the majority of patients are in the late stage at initial diagnosis. Long non-coding RNAs (LncRNAs), a novel type of non-coding RNA, have recently been recognized as critical factors in tumor initiation and progression, but the role of exosomal LncRNAs has not been thoroughly excavated in NSCLC yet. METHODS We isolated exosomes from the serum of patients with NSCLC and healthy controls. Exosome RNA deep sequencing was subsequently performed to detect differentially expressed exosomal LncRNAs. qRT-PCR assay was then utilized to validate dysregulated LncRNAs in both testing and multicentric validation cohort. Receiver operating characteristic (ROC) curve was used to detect the diagnostic capability of exosomal biomarkers. Furthermore, Kaplan-Meier analysis was applied to evaluate the prognostic values of these molecules. RESULTS On the basis of analysis, we found that novel exosomal LncRNA RP5-977B1 exhibited higher levels in NSCLC than that in the healthy controls. The area under the curve (AUC) value of exosomal RP5-977B1 was 0.8899 and superior to conventional biomarkers CEA and CYFRA21-1 both in testing and multicentric validation cohort. Interestingly, the diagnostic capability of exosomal RP5-977B1 was also validated in early-stage patients with NSCLC. Furthermore, high expression of exosomal RP5-977B1was closely related with worse prognosis in NSCLC (P = 0.036). CONCLUSIONS Our results suggested that exosomal RP5-977B1 might serve as a novel "liquid biopsy" diagnostic and prognostic biomarker to monitor NSCLC and improve possible therapy.
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Affiliation(s)
- Ling Min
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China.,Department of Laboratory Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Ting Zhu
- Department of Laboratory Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Bo Lv
- Department of General Practice, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080, Guangdong, China
| | - Taixue An
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China
| | - Qichao Zhang
- Department of Laboratory Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Yanyan Shang
- Department of Laboratory Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Zhiwu Yu
- Department of Laboratory Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
| | - Lei Zheng
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China
| | - Qian Wang
- Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhouda Road, Guangzhou, 510515, Guangdong, China.
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Neuron-Specific Enolase and Hemoglobin as Risk Factors of Intraocular Metastasis in Patients with Renal Cell Carcinoma. DISEASE MARKERS 2022; 2022:2883029. [PMID: 35502301 PMCID: PMC9056261 DOI: 10.1155/2022/2883029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 03/17/2022] [Accepted: 03/31/2022] [Indexed: 11/17/2022]
Abstract
Renal cell carcinoma (RCC) appears to be a high risk of spread. This research investigated the correlation between a different range of clinical features and intraocular metastasis (IOM) in RCC patients and attempted to determine potential risk factors of RCC patients with IOM. In the study, there are a total of 351 patients with RCC that were recruited between May 1994 and May 2016. The differences between RCC patients with IOM and RCC patients with non-IOM (NIOM) were evaluated by the chi-squared test and Student t test. Binary logistic regression analysis was applied to determine risk factors. Finally, the value of diagnosis for RCC patients with IOM was assessed by receiver operating characteristic (ROC) curve analysis. Eighteen individuals were identified with IOM. There were no significant differences that were detected in alkaline phosphatase (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP), cancer antigen 125 (CA-125), cancer antigen 153 (CA-153), cancer antigen 199 (CA-199), calcium, age, primary tumor site, and histopathological subtypes between the two groups. But there was a difference in terms of gender (
). The IOM group exhibited significantly higher neuron-specific enolase (NSE) and lower hemoglobin (Hb) values compared to the NIOM group (
, respectively). Binary logistic regression identified NSE and Hb as significant risk factors of IOM for RCC patient (
and
, respectively). The ROC curve analysis indicated that the area under the curve (AUC) values of NSE and Hb were 0.694 and 0.749, while cut-off values were 49.5 ng/mL and 102.5 g/L, respectively. The sensitivity and specificity of NSE were 72.2% and 66.4%, respectively, while those of Hb were 72.2% and 74.2%, respectively. The result reveals that NSE and Hb represent promising significant risk factors of IOM for RCC patients. Notably, Hb is more reliable than NSE in distinguishing case of IOM from NIOM in patients with RCC.
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Yang H, Chen H, Zhang G, Li H, Ni R, Yu Y, Zhang Y, Wu Y, Liu H. Diagnostic value of circulating genetically abnormal cells to support computed tomography for benign and malignant pulmonary nodules. BMC Cancer 2022; 22:382. [PMID: 35397524 PMCID: PMC8994303 DOI: 10.1186/s12885-022-09472-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The accuracy of CT and tumour markers in screening lung cancer needs to be improved. Computer-aided diagnosis has been reported to effectively improve the diagnostic accuracy of imaging data, and recent studies have shown that circulating genetically abnormal cell (CAC) has the potential to become a novel marker of lung cancer. The purpose of this research is explore new ways of lung cancer screening.
Methods
From May 2020 to April 2021, patients with pulmonary nodules who had received CAC examination within one week before surgery or biopsy at First Affiliated Hospital of Zhengzhou University were enrolled. CAC counts, CT scan images, serum tumour marker (CEA, CYFRA21–1, NSE) levels and demographic characteristics of the patients were collected for analysis. CT were uploaded to the Pulmonary Nodules Artificial Intelligence Diagnostic System (PNAIDS) to assess the malignancy probability of nodules. We compared diagnosis based on PNAIDS, CAC, Mayo Clinic Model, tumour markers alone and their combination. The combination models were built through logistic regression, and was compared through the area under (AUC) the ROC curve.
Results
A total of 93 of 111 patients were included. The AUC of PNAIDS was 0.696, which increased to 0.847 when combined with CAC. The sensitivity (SE), specificity (SP), and positive (PPV) and negative (NPV) predictive values of the combined model were 61.0%, 94.1%, 94.7% and 58.2%, respectively. In addition, we evaluated the diagnostic value of CAC, which showed an AUC of 0.779, an SE of 76.3%, an SP of 64.7%, a PPV of 78.9%, and an NPV of 61.1%, higher than those of any single serum tumour marker and Mayo Clinic Model. The combination of PNAIDS and CAC exhibited significantly higher AUC values than the PNAIDS (P = 0.009) or the CAC (P = 0.047) indicator alone. However, including additional tumour markers did not significantly alter the performance of CAC and PNAIDS.
Conclusions
CAC had a higher diagnostic value than traditional tumour markers in early-stage lung cancer and a supportive value for PNAIDS in the diagnosis of cancer based on lung nodules. The results of this study offer a new mode of screening for early-stage lung cancer using lung nodules.
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Li Z, Wu W, Pan X, Li F, Zhu Q, He Z, Chen L. Serum tumor markers level and their predictive values for solid and micropapillary components in lung adenocarcinoma. Cancer Med 2022; 11:2855-2864. [PMID: 35289087 PMCID: PMC9302275 DOI: 10.1002/cam4.4645] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 01/13/2022] [Accepted: 01/19/2022] [Indexed: 12/23/2022] Open
Abstract
Background This study aims to reveal the serum tumor marker (STM) levels in lung adenocarcinoma (LUAD) histological subtypes and evaluate their values in predicting the solid and micropapillary components (SMC). Methods We retrospectively analyzed 3100 invasive LUAD patients between January 2017 and December 2020. Associations between preoperative STMs (CEA, CYFRA21‐1, CA199, CA724, NSE, AFP) and LUAD subtypes were evaluated. Multivariate regression analyses were used to determine the independent predictors. Predictive models for SMC were constructed and AUC (area under the curve) was calculated. Results CEA and CYFRA21‐1 levels differed across the LUAD histological subtypes, with the SPA (solid‐predominant adenocarcinoma) having the highest level and the LPA (lepidic‐predominant adenocarcinoma) harboring the lowest level (p <0.001). Tumors with SMC also had higher CEA and CYFRA21‐1 levels than those absence of SMC. Gender, tumor size, CEA, Ki‐67, EGFR mutation (solid components only), and tumor differentiation were significantly independently associated with the containing of SMC. Patients were split into two data sets (training set: 2017–2019 and validation set: 2020). The model with gender and tumor size yielded an AUC of 0.723 (training set) and 0.704 (validation set) for the solid component. Combination of CEA, gender, and tumor size led to a significant increase in the predictive accuracy (training set: 0.771, p = 0.009; validation set: 0.747, p = 0.034). The AUC of the model for micropapillary component with only gender and tumor size was 0.699 and 0.711 in the training set and validation set, respectively. Integration of CEA with gender and tumor size significantly improved the predictive performance with an AUC of 0.746 (training set, p = 0.045) and 0.753 (validation set, p <0.001). Conclusion Serum CEA and CYFRA21‐1 varied considerably according to LUAD histological subtypes. The combination of serum CEA and other factors showed prominent values in predicting the SMC.
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Affiliation(s)
- Zhihua Li
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weibing Wu
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xianglong Pan
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fang Li
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Zhu
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhicheng He
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Liang Chen
- Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Zhang Y, Chen Z, Jiang A, Gao G. KLRK1 as a prognostic biomarker for lung adenocarcinoma cancer. Sci Rep 2022; 12:1976. [PMID: 35132098 PMCID: PMC8821622 DOI: 10.1038/s41598-022-05997-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is one of the most common malignancy worldwide and causes estimated 1.6 million deaths each year. Cancer immunosurveillance has been found to play an important role in lung cancer and may be related with its prognosis. KLRK1, encoding NKG2D, is a homodimeric lectin-like receptor. However, there has not been one research of KLRK1 as a biomarker in lung cancer. Data including patients` clinical characteristics and RNAseq information of KLRK1 from TCGA were downloaded. A total of 1019 patients with lung cancer were included in this study, among which 407 patients were female and 611 patients were male. Evaluations of mRNA expression, diagnostic value by ROC (receiver operating characteristic) curves and prognostic value by survival curve, Cox model and subgroup analysis were performed. The level of KLRK1 expression in lung adenocarcinoma cancer tissues and normal lung tissues was detected by qRT-PCR. The CCK-8 assay investigated the proliferation rate and the wound healing assay assessed the migratory ability in vitro. The expression of KLRK1 in tumor was lower than that in normal tissue. KLRK1 expression was associated with gender, histologic grade, stage, T classification and vital status. Patients with high KLRK1 expression presented an improved overall survival (P = 0.0036) and relapse free survival (P = 0.0031). KLRK1 was found to have significant prognostic value in lung adenocarcinoma (P = 0.015), stage I/II (P = 0.03), older patients (P = 0.0052), and male (P = 0.0047) by subgroup overall survival analysis, and in lung adenocarcinoma (P = 0.0094), stage I/II (P = 0.0076), older patients (P = 0.0072), and male (P = 0.0033) by subgroup relapse free survival analysis. Lung adenocarcinoma cancer patients with high KLRK1 expression presented an improved overall survival (P = 0.015) and relapse free survival (P = 0.0094). In vitro studies indicated that KLRK1 inhibited tumor cell proliferation and migration. KLRK1 was an independent prognostic factor and high KLRK1 expression indicated a better overall and relapse free survival. KLRK1 may be a prognostic biomarker for lung adenocarcinoma cancer.
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Affiliation(s)
- Yanan Zhang
- Clinical Medical College, Weifang Medical University, Weifang, 261000, China.,Linyi People's Hospital, Linyi, 276000, China
| | - Zeyang Chen
- Clinical Medical College, Qingdao University, Qingdao, 266000, China
| | - Aifang Jiang
- Weifang Medical University, Weifang, 261000, China.
| | - Guanqi Gao
- Linyi People's Hospital, Linyi, 276000, China.
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Luo Y, Zhang Q, Lv B, Shang Y, Li J, Yang L, Yu Z, Luo K, Deng X, Min L, Zhu T. CircFOXP1: A novel serum diagnostic biomarker for non-small cell lung cancer. Int J Biol Markers 2022; 37:58-65. [PMID: 35072545 DOI: 10.1177/17246008211073151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Emerging evidence suggests that circular RNAs (circRNAs) were aberrantly expressed in the patients of non-small cell lung cancer (NSCLC). This study aims to evaluate the diagnostic value of potential serum biomarker in circRNAs. Methods Serum circRNAs were extracted and purified by RNA isolated kit and identified by quantitative real time-polymerase chain reaction (qRT-PCR) assay. We then performed a receiver operating characteristic (ROC) curve to estimate the diagnostic efficacy. The relationship between circRNA and clinic characteristics of patients was analyzed by SPSS 25.0. Univariate and multivariate analyses were also used to evaluate its diagnostic capability. The mechanism of circFOXP1 was further excavated by bioinformatics analysis. Results By performing qRT-PCR assay, we identified that circFOXP1 (hsa_circ_0008234) and conventional tumor markers (carcinoembryonic antigen (CEA) and cytokeratin fragment 21–1 (CYFRA21-1)) were all significantly overexpressed in the serum of patients with NSCLC when compared with healthy controls ( P < 0.05). While the ROC curves analysis demonstrated that area under the curve of circFOXP1 was obviously superior to CEA and CYFRA21-1, which exerted more diagnostic advantage. Univariate and multivariate analyses revealed that serum circFOXP1 was an independent diagnostic molecule, and was significantly correlated with T stage and lymphatic metastasis in NSCLC ( P < 0.05). Mechanistically, circFOXP1 might target hsa-miR-370-3p and hsa-miR-18a-5p, and be involved in vascular endothelial growth factor signaling pathways to regulate proliferative and metastasis processes. Conclusion Our results highlight the preferable diagnostic potential of serum circFOXP1 in NSCLC.
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Affiliation(s)
- Yirong Luo
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
- KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medial University, Guangzhou, China
| | - Qichao Zhang
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Bo Lv
- Department of General Practice, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangdong, China
| | - Yanyan Shang
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Juan Li
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Lina Yang
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Zhiwu Yu
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Kai Luo
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Xiaoyan Deng
- KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medial University, Guangzhou, China
| | - Ling Min
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Ting Zhu
- Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
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Zhang X, Li J, Wang Y, Liu M, Liu F, Zhang X, Pei L, Wang T, Jiang D, Wang X, Zhang J, Dai L. A Diagnostic Model With IgM Autoantibodies and Carcinoembryonic Antigen for Early Detection of Lung Adenocarcinoma. Front Immunol 2022; 12:728853. [PMID: 35140701 PMCID: PMC8818794 DOI: 10.3389/fimmu.2021.728853] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 12/28/2021] [Indexed: 12/19/2022] Open
Abstract
Immunoglobulin M (IgM) autoantibodies, as the early appearing antibodies in humoral immunity when stimulated by antigens, might be excellent biomarkers for the early detection of lung cancer (LC). We aimed to develop a multi-analyte integrative model combining IgM autoantibodies and a traditional tumor biomarker that could be a valuable and powerful auxiliary diagnostic tool and might improve the accuracy of early detection of lung adenocarcinoma (LUAD). A customized protein array based on cancer driver genes was constructed and applied in the discovery cohort consisting of 68 LUAD patients and 68 normal controls (NCs); 31 differentially expressed IgM autoantibodies were identified. The top 5 candidate IgM autoantibodies [based on the area under the receiver operating characteristic curve (AUC) ranking], namely, TSHR, ERBB2, survivin, PIK3CA, and JAK2, were validated in the validation cohort using enzyme-linked immunosorbent assay (ELISA), which included 147 LUAD samples, 72 lung squamous cell carcinoma (LUSC) samples, 44 small cell lung carcinoma (SCLC) samples, and 147 NCs. These indicators presented diagnostic capacity for LUAD, with AUCs of 0.599, 0.613, 0.579, 0.601, and 0.633, respectively (p < 0.05). However, none of them showed a significant difference between the SCLC and NC groups, and only the IgM autoantibody against JAK2 showed a higher expression in LUSC than in NC (p = 0.046). Through logistic regression analysis, with the five IgM autoantibodies and carcinoembryonic antigen (CEA), one diagnostic model was constructed for LUAD. The model yielded an AUC of 0.827 (sensitivity = 56.63%, specificity = 93.98%). The diagnostic efficiency was superior to that of either CEA (AUC = 0.692) or IgM autoantibodies alone (AUC = 0.698). Notably, the accuracy of this model in early-stage LUAD reached 83.02%. In conclusion, we discovered and identified five novel IgM indicators and developed a multi-analyte model combining IgM autoantibodies and CEA, which could be a valuable and powerful auxiliary diagnostic tool and might improve the accuracy of early detection of LUAD.
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Affiliation(s)
- Xue Zhang
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Jiaqi Li
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Yulin Wang
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Man Liu
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Fenghui Liu
- Department of Respiratory and Sleep Medicine in the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Xiuzhi Zhang
- Department of Pathology, Henan Medical College, Zhengzhou, China
| | - Lu Pei
- Department of Clinical Laboratory, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, China
| | - Tingting Wang
- Department of Clinical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
| | - Di Jiang
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Xiao Wang
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Jianying Zhang
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences & School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, China
- *Correspondence: Liping Dai,
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Ju M, Ge X, Di X, Zhang Y, Liang L, Shi Y. Diagnostic, Prognostic, and Recurrence Monitoring Value of Plasma CYFRA21-1 and NSE Levels in Patients With Esophageal Squamous Cell Carcinoma. Front Oncol 2022; 11:789312. [PMID: 35127494 PMCID: PMC8813736 DOI: 10.3389/fonc.2021.789312] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 12/31/2021] [Indexed: 01/06/2023] Open
Abstract
This study was aimed to evaluate the clinical values of single markers and combination in the diagnosis, short-term efficacy and recurrence risk assessment of esophageal squamous cell carcinoma (ESCC).
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Affiliation(s)
- Mengyang Ju
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Xiaolin Ge
- Department of Radiotherapy, Jiangsu Provincial People’s Hospital, Nanjing, China
| | - Xiaoke Di
- Department of Radiotherapy, Jiangsu Provincial People’s Hospital, Nanjing, China
| | - Yumeng Zhang
- Department of Oncology, Graduate School of Nanjing Medical University, Nanjing, China
| | - Liang Liang
- Department of Oncology, The People’s Hospital of Jurong City, Zhenjiang, China
| | - Yujing Shi
- Department of Oncology, The People’s Hospital of Jurong City, Zhenjiang, China
- *Correspondence: Yujing Shi,
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Zhu C, Zhang N, Zhong A, Xiao K, Lu R, Guo L. A combined strategy of TK1, HE4 and CA125 shows better diagnostic performance than risk of ovarian malignancy algorithm (ROMA) in ovarian carcinoma. Clin Chim Acta 2022; 524:43-50. [PMID: 34813778 DOI: 10.1016/j.cca.2021.11.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 10/19/2021] [Accepted: 11/17/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND The dual marker algorithm Risk of Ovarian Malignancy Algorithm (ROMA) has been widely used in the clinic for the identification of equivocal pelvic masses in ovarian carcinoma. To obtain higher diagnostic efficiency, we created a new diagnostic index, Risk of Ovarian Malignancy Index (ROMI), by combing thymidine kinase 1 (TK1), HE4 and CA125. METHODS 335 patients with pelvic masses on imaging and 46 healthy controls were enrolled. Serum TK1 was analyzed before further study. ROMI and ROMA were evaluated for diagnostic efficiency. RESULTS The level of TK1 was elevated in malignant ovarian tumors compared to benign masses (p < 0.001) and healthy controls (p < 0.001). TK1 expression was positively correlated with stage, intrapelvic metastasis, lymphatic metastasis and distant metastasis (all p values < 0.001). The area under the receiver operating characteristic curve (AUC) of ROMI was higher than that of ROMA for both pre- and postmenopausal women. ROMI had better sensitivity, specificity, accuracy, and positive and negative predictive values than ROMA in diagnosis of all-stage or stage I + II ovarian carcinoma for both pre- and postmenopausal women. CONCLUSIONS TK1 is a potential biomarker in detection of ovarian carcinoma. ROMI shows better diagnostic performance than ROMA in distinguishing malignant ovarian tumors from benign masses.
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Affiliation(s)
- Cheng Zhu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Nenghua Zhang
- Department of Clinical Laboratory, Municipal Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Ailing Zhong
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Kangjia Xiao
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Renquan Lu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Lin Guo
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Zhang C, Chang L, Yao Y, Chao C, Ge Z, Fan C, Yu H, Wang B, Yang J. Role of the CBX Molecular Family in Lung Adenocarcinoma Tumorigenesis and Immune Infiltration. Front Genet 2021; 12:771062. [PMID: 34966411 PMCID: PMC8710700 DOI: 10.3389/fgene.2021.771062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/22/2021] [Indexed: 12/02/2022] Open
Abstract
Background: The members of the Chromobox (CBX) family are important epigenetic regulatory molecules with critical biological roles in many tumors. However, no study has analyzed or verified their role in lung adenocarcinoma (LUAD). Methods: UALCAN and Oncomine databases were used to analyze CBX expression in LUAD, and the cBioPortal database was used to analyze CBX genetic variations. The Kaplan-Meier plotter and UALCAN databases were used to identify molecules with prognostic value. Gene Ontology pathway, receiver operating characteristic curves, and tumor-infiltrating immune cell analyses were used to clarify the biological function of the CBX hub molecules. Paired tumor samples and lung adenocarcinoma cell lines were collected for molecular functional assays to validate the results of the bioinformatics analysis. Results: CBX3/5 may have a cancer-promoting effect and its expression is associated with a poor patient prognosis, while CBX7 shows an opposite trend. CBX3/5/7 can regulate signaling pathways, regulate tumor immune cell infiltration, and has diagnostic value. Molecular biology experiments show that CBX3/5 is highly expressed in LUAD patients; in vitro it promotes the proliferation and migration of the LUAD cell line and can regulate the expression of the corresponding cytokines. CBX7 has opposite effects. Conclusion: Our bioinformatics analysis and subsequent experimental verification confirmed the CBX family members acted as hub signaling molecules in LUAD. The results provide new potential targets for the diagnosis and treatment of this cancer.
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Affiliation(s)
- Chun Zhang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Lisha Chang
- Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Yizhen Yao
- Department of Respiratory Medicine, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, China
| | - Ce Chao
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Zhongchun Ge
- Department of Cardiology, People's Hospital of Xuyi, Xuyi, China
| | - Chengfeng Fan
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Hualin Yu
- Department of Radiotherapy, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Bin Wang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jingsong Yang
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Jing R, Wang J, Li J, Wang X, Li B, Xue F, Shao G, Xue H. A wavelet features derived radiomics nomogram for prediction of malignant and benign early-stage lung nodules. Sci Rep 2021; 11:22330. [PMID: 34785692 PMCID: PMC8595377 DOI: 10.1038/s41598-021-01470-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 10/27/2021] [Indexed: 11/09/2022] Open
Abstract
This study was to develop a radiomics nomogram mainly using wavelet features for identifying malignant and benign early-stage lung nodules for high-risk screening. A total of 116 patients with early-stage solitary pulmonary nodules (SPNs) (≤ 3 cm) were divided into a training set (N = 70) and a validation set (N = 46). Radiomics features were extracted from plain LDCT images of each patient. A radiomics signature was then constructed with the LASSO with the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. This radiomics signature, consisting of one original and nine wavelet features, achieved favorable predictive efficacy than Mayo Clinic Model. The radiomics nomogram with radiomics signature and age also showed good calibration and discrimination in the training set (AUC 0.9406; 95% CI 0.8831-0.9982) and the validation set (AUC 0.8454; 95% CI 0.7196-0.9712). The decision curve indicated the clinical usefulness of our nomogram. The presented radiomics nomogram shows favorable predictive accuracy for identifying malignant and benign lung nodules in early-stage patients and is much better than the Mayo Clinic Model.
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Affiliation(s)
- Rui Jing
- Department of Radiology, Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Jingtao Wang
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, People's Republic of China
| | - Jiangbing Li
- Department of Cardiology, Shandong Provincial Hospital, Jinan, Shandong, People's Republic of China
| | - Xiaojuan Wang
- Department of Radiology, Second Hospital of Shandong University Zhaoyuan Branch, Zhaoyuan, Shandong, People's Republic of China
| | - Baijie Li
- Department of Radiology, Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Fuzhong Xue
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, People's Republic of China
| | - Guangrui Shao
- Department of Radiology, Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
| | - Hao Xue
- Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
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Lv X, Bi M, Xu X, Li Y, Geng C, Cui B, Fang Y. An ultrasensitive ratiometric immunosensor based on the ratios of conjugated distyrylbenzene derivative nanosheets with AIECL properties and electrochemical signal for CYFRA21-1 detection. Anal Bioanal Chem 2021; 414:1389-1402. [PMID: 34741181 DOI: 10.1007/s00216-021-03764-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/25/2021] [Accepted: 10/28/2021] [Indexed: 02/04/2023]
Abstract
Aggregation-induced electrochemiluminescence reagent, a distyrylbenzene derivative with donor-acceptor conjugated nanosheet structure, namely TPAPCN, was used as a trace label and modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody in this work. In aggregate state, TPAPCN with twisted structure was limited in nanometer space through intermolecular π - π stacking interactions, which not only restricts the intramolecular motions but also combines a large number of singlet excitons to greatly trigger electrochemiluminescence (ECL). The ECL signal of this system enhanced with more captured cytokeratin 19 fragment 21-1 (CYFRA21-1) on the modified electrode. Three-dimensional graphene/platinum nanoparticles with large specific surface, and excellent electroconductivity and biocompatibility were prepared and acted as excellent carriers for thionine handling (3D-GN/PtNPs/Th), which was employed for improving the loading of antibodies and generating internal electrochemical signal. Consequently, a novel ratiometric sandwich immunosensor for CYFRA21-1 detection was fabricated based on TPAPCN and 3D-GN/PtNPs/Th, that is, a rapid and reliable detection was achieved through the ratio between ECL and electrochemical signals. The prepared sensor performed good linearity in the range of 50 fg/mL to 1 ng/mL with a detection limit as low as 16 fg/mL. Moreover, the detection results revealed well in the analysis of human serum samples, demonstrating a significant application for clinical monitoring and biomolecules detection.
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Affiliation(s)
- Xiaoyi Lv
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China
| | - Mengmeng Bi
- Juye County People's Hospital, Heze, 274900, Shandong, People's Republic of China
| | - Xiaoyun Xu
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China
| | - Yanping Li
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China
| | - Chao Geng
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China
| | - Bo Cui
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China
| | - Yishan Fang
- State Key Laboratory of Biobased Material and Green Papermaking, School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, Shandong, China.
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Šutić M, Vukić A, Baranašić J, Försti A, Džubur F, Samaržija M, Jakopović M, Brčić L, Knežević J. Diagnostic, Predictive, and Prognostic Biomarkers in Non-Small Cell Lung Cancer (NSCLC) Management. J Pers Med 2021; 11:1102. [PMID: 34834454 PMCID: PMC8624402 DOI: 10.3390/jpm11111102] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/21/2021] [Accepted: 10/25/2021] [Indexed: 12/25/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the "one-fits-all" paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.
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Affiliation(s)
- Maja Šutić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Ana Vukić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Jurica Baranašić
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
| | - Asta Försti
- Hopp Children’s Cancer Center (KiTZ), 69120 Heidelberg, Germany;
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Feđa Džubur
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Miroslav Samaržija
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Marko Jakopović
- German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; (F.D.); (M.S.); (M.J.)
- Clinical Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Luka Brčić
- Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria;
| | - Jelena Knežević
- Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.Š.); (A.V.); (J.B.)
- Faculties for Dental Medicine and Health, University of Osijek, 31000 Osijek, Croatia
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Shang L, Zhang W, Wu H, Wu R, Chen R. Diagnostic Value of FTO Combined with CEA or CYFRA21-1 in Nonsmall Cell Lung Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:1436088. [PMID: 34691202 PMCID: PMC8531790 DOI: 10.1155/2021/1436088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/04/2021] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To explore the diagnostic value of FTO combined with CEA or CYFRA21-1 for nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for molecular diagnosis of NSCLC. METHODS Totally, 60 patients with nonsmall cell lung cancer (NSCLC) treated in our hospital between Feb. 2018 and Feb. 2019 were enrolled into the patient group (Pat group) and 50 healthy individuals with normal physical examination results in our hospital over the same time span into the control group (Con group). Serum of each participant was collected, and then qRT-PCR was adopted for quantification of serum FTO and the chemiluminescence method for quantification of serum CEA and CYFRA21-1. Additionally, corresponding ROC curves were drawn for diagnostic value analyses of FTO, CEA, and CYFRA21-1 in NSCLC and Cox regression analysis was performed for analysis of independent factors impacting the patients' 3-year prognosis. RESULTS The Pat group presented notably higher FTO, CEA, and CYFRA21-1 levels than the Con group (all P < 0.05), and patients with a high FTO level faced notably higher probabilities of stage III + IV and lymph node metastasis (LNM) (both P < 0.05). Additionally, according to ROC curve-based analysis, with a high level in patients with NSCLC, FTO had high specificity and sensitivity in diagnosing NSCLC; joint detection of it with CEA or CYFRA21-1 demonstrated a higher sensitivity in NSCLC diagnosis and presented a higher specificity in diagnosing early NSCLC compared with detection of CEA or CYFRA21-1 alone. According to Cox regression analysis, clinical stage, LNM, and FTO were independent risk factors impacting the prognosis of patients with LC (all P < 0.05). CONCLUSION FTO presents a high level in NSCLC cases, and joint detection of it with CEA or CYFRA21-1 delivered a higher specificity in diagnosing NSCLC in contrast to detection of CEA or CYFRA21-1 alone, so the joint detection is worth popularizing in clinical scenarios.
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Affiliation(s)
- Liqun Shang
- Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xian 710068, China
| | - Wei Zhang
- Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xian 710068, China
| | - Hua Wu
- Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xian 710068, China
| | - Runmiao Wu
- Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xian 710068, China
| | - Ruilin Chen
- Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xian 710068, China
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Fu Y, Xue P, Li N, Zhao P, Xu Z, Ji H, Zhang Z, Cui W, Dong E. Fusion of 3D lung CT and serum biomarkers for diagnosis of multiple pathological types on pulmonary nodules. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2021; 210:106381. [PMID: 34496322 DOI: 10.1016/j.cmpb.2021.106381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 08/24/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND AND OBJECTIVE Current researches on pulmonary nodules mainly focused on the binary-classification of benign and malignant pulmonary nodules. However, in clinical applications, it is not enough to judge whether pulmonary nodules are benign or malignant. In this paper, we proposed a fusion model based on the Lung Information Dataset Containing 3D CT Images and Serum Biomarkers (LIDCCISB) we constructed to accurately diagnose the types of pulmonary nodules in squamous cell carcinoma, adenocarcinoma, inflammation and other benign diseases. METHODS Using single modal information of lung 3D CT images and single modal information of Lung Tumor Biomarkers (LTBs) in LIDCCISB, a Multi-resolution 3D Multi-classification deep learning model (Mr-Mc) and a Multi-Layer Perceptron machine learning model (MLP) were constructed for diagnosing multiple pathological types of pulmonary nodules, respectively. To comprehensively use the double modal information of CT images and LTBs, we used transfer learning to fuse Mr-Mc and MLP, and constructed a multimodal information fusion model that could classify multiple pathological types of benign and malignant pulmonary nodules. RESULTS Experiments showed that the constructed Mr-Mc model can achieve an average accuracy of 0.805 and MLP model can achieve an average accuracy of 0.887. The fusion model was verified on a dataset containing 64 samples, and achieved an average accuracy of 0.906. CONCLUSIONS This is the first study to simultaneously use CT images and LTBs to diagnose multiple pathological types of benign and malignant pulmonary nodules, and experiments showed that our research was more advanced and more suitable for practical clinical applications.
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Affiliation(s)
- Yu Fu
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China
| | - Peng Xue
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China
| | - Ning Li
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Peng Zhao
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Zhuodong Xu
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Huizhong Ji
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China
| | - Zhili Zhang
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China
| | - Wentao Cui
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China.
| | - Enqing Dong
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai 264209, China.
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High CTSL2 expression predicts poor prognosis in patients with lung adenocarcinoma. Aging (Albany NY) 2021; 13:22315-22331. [PMID: 34555812 PMCID: PMC8507295 DOI: 10.18632/aging.203540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 09/03/2021] [Indexed: 11/25/2022]
Abstract
Cathepsin like 2 (CTSL2) is a lysosomal cysteine protease, and may be associated with tumor metastasis. However, CTSL2 has not been reported as a biomarker in lung adenocarcinoma (LUAD). In this study, bioinformatics analysis using data from The Cancer Genome Atlas was performed. Wilcoxon rank-sum test and chi-square test were carried out. Kaplan-Meier and Cox regression were performed to evaluate the effect of CTSL2 expression in the overall survival. Our results indicated that CTSL2 in tumor was significantly higher than that in normal tissue (P < 0.001). High CTSL2 expression was significantly associated with age (P = 0.02), vital status (P < 0.001), and T classification (P = 0.03), and correlated with poor overall survival (HR = 1.62, 95% CI = 1.21–2.18, P = 0.001). CTSL2 expression was an independent risk factor for overall survival in patients with LUAD (HR = 1.52, 95% CI = 1.12–2.05, P = 0.006). A nomogram was plotted for illustration of CTSL2 expression on the risk of LUAD. Furthermore, in vitro cell experiments showed the CTSL2 promoted the proliferation and migration of A549 cells. In summary, high CTSL2 expression predicts poor prognosis in patients with LUAD.
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Zhang JH, Shen Q, Zhou YG. Quantification of Tumor Protein Biomarkers from Lung Patient Serum Using Nanoimpact Electrochemistry. ACS Sens 2021; 6:2320-2329. [PMID: 34033456 DOI: 10.1021/acssensors.1c00361] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Protein quantification with high throughput and high sensitivity is essential in the early diagnosis and elucidation of molecular mechanisms for many diseases. Conventional approaches for protein assay often suffer from high costs, long analysis time, and insufficient sensitivity. The recently emerged nanoimpact electrochemistry (NIE), as a contrast, allows in situ detection of analytes one at a time with simplicity, fast response, high throughput, and the potential of reducing the detection limits down to the single entity level. Herein, we propose a NIE-enabled electrochemical immunoassay using silver nanoparticles (AgNPs) as labels for the detection of CYFRA21-1, a typical protein marker for lung carcinoma. This strategy is based on the measurement of the impact frequency and the charge intensity of the electrochemical oxidation of individual AgNPs before and after they are modified with anti-CYFRA21-1 and in turn immunocomplexed with CYFRA21-1. Both the frequency and intensity modes of single-nanoparticle electrochemistry correlate well with each other, resulting in a self-validated immunoassay that provides linear ranges of two orders of magnitude and a limit of detection of 0.1 ng/mL for CYFRA21-1 analysis. The proposed immunoassay also exhibits excellent specificity when challenged with other possible interfering proteins. In addition, the CYFRA21-1 content is validated by a conventional, well-known enzyme-linked immunosorbent assay and successfully quantified in a diluted healthy serum with a satisfactory recovery. Moreover, CYFRA21-1 detection in serum samples of lung cancer patients is successfully demonstrated, suggesting the feasibility of the NIE-based immunoassay in clinically relevant diagnosis. To the best of our knowledge, this is the first report to construct NIE-based electrochemical immunoassays for the specific detection of tumor protein biomarkers.
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Affiliation(s)
- Jian-Hua Zhang
- Institute of Chemical Biology and Nanomedicine (ICBN), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Qian Shen
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China
| | - Yi-Ge Zhou
- Institute of Chemical Biology and Nanomedicine (ICBN), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
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Yuan G, Xie H, Wei T, Zhu D, Zhang C, Yang Y. Diagnostic potential of extracellular vesicle-associated microRNA-10b and tumor markers for lung adenocarcinoma. Oncol Lett 2021; 22:614. [PMID: 34257722 PMCID: PMC8243083 DOI: 10.3892/ol.2021.12875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 05/21/2021] [Indexed: 11/05/2022] Open
Abstract
MicroRNAs (miRNAs/miRs) in extracellular vesicles (EVs) are potential diagnostic markers. The purpose of the present study was to investigate potential EV miRNA biomarkers for lung adenocarcinoma (LUAD). Potential miRNAs were identified by searching public databases and verified by examining clinical samples. The diagnostic value of EV-associated miR-10b, plasma miR-10b and tumor markers (TMs), including α-fetoprotein (AFP), neuron-specific enolase, carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA211), pro-gastrin-releasing-peptide, carbohydrate antigen (CA)125, CA153, CA199 and CA724, was evaluated via receiver operating characteristic curve analysis. By searching the Gene Expression Omnibus and The Cancer Genome Atlas databases, miR-10b was identified as a potential biomarker. The analysis of clinical samples suggested that EV-associated miR-10b from plasma was significantly differentially expressed between LUAD and control samples. EV-associated miR-10b could function as a diagnostic marker for LUAD, with an AUC of 0.998, which was higher than the AUCs for TMs such as AFP, CEA, CYFRA211, CA125, CA153, CA199, CA724, pro-gastrin-releasing-peptide and neuron-specific enolase. In conclusion, EV-associated miR-10b may be a potential diagnostic biomarker for LUAD that is superior to plasma miR-10b and TMs.
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Affiliation(s)
- Guangda Yuan
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Hongya Xie
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Tengteng Wei
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Donglin Zhu
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Chuanyu Zhang
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
| | - Yong Yang
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China
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Ma YS, Shi BW, Guo JH, Liu JB, Yang XL, Xin R, Shi Y, Zhang DD, Lu GX, Jia CY, Wang HM, Wang PY, Yang HQ, Zhang JJ, Wu W, Cao PS, Yin YZ, Gu LP, Tian LL, Lv ZW, Wu CY, Wang GR, Yu F, Hou LK, Jiang GX, Fu D. microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer. Carcinogenesis 2021; 42:762-771. [PMID: 33758932 DOI: 10.1093/carcin/bgab023] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 02/19/2021] [Accepted: 03/23/2021] [Indexed: 12/25/2022] Open
Abstract
We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.
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Affiliation(s)
- Yu-Shui Ma
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China.,Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, P.R. China
| | - Bo-Wen Shi
- Department of Thoracic Surgery, Navy Military Medical University Affiliated Changhai Hospital, Shanghai, P.R. China
| | - Jun-Hong Guo
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Ji-Bin Liu
- Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, P.R. China
| | - Xiao-Li Yang
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Rui Xin
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Yi Shi
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Dan-Dan Zhang
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Gai-Xia Lu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Cheng-You Jia
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Hui-Min Wang
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Pei-Yao Wang
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Hui-Qiong Yang
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Jia-Jia Zhang
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Wei Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Ping-Sheng Cao
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Yu-Zhen Yin
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Li-Peng Gu
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Lin-Lin Tian
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Zhong-Wei Lv
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Chun-Yan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Gao-Ren Wang
- Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, P.R. China
| | - Fei Yu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Li-Kun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Geng-Xi Jiang
- Department of Thoracic Surgery, Navy Military Medical University Affiliated Changhai Hospital, Shanghai, P.R. China
| | - Da Fu
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China
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