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Sun AH, Zhang XY, Huang YY, Chen L, Wang Q, Jiang XC. Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients. World J Clin Oncol 2024; 15:1033-1047. [PMID: 39193154 PMCID: PMC11346068 DOI: 10.5306/wjco.v15.i8.1033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/03/2024] [Accepted: 07/24/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients. However, few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators. AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients. METHODS From October 2018 to April 2020, a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study. The relationship between serum tumor markers and clinical and pathological data were analyzed. We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis. Overall survival (OS) was also compared across different stages of gastric cancer. RESULTS The deadline for follow-up was May 31, 2023. A total of 1236 patients were included in our study. Univariate analysis found that age, clinical stage, T and N stage, tumor location, differentiation, Borrmann type, size, and four serum tumor markers were prognostic factors of OS (P < 0.05). It was shown that clinical stage, tumor size, alpha foetoprotein, carcinoembryonic antigen, CA125 and CA19-9 (P < 0.05) were independent prognostic factors for OS. According to the scoring results obtained from the statistical model, we found that patients with high scores had poorer survival time (P < 0.05). Furthermore, in stage I patients, the 3-year OS for scores 0-3 ranged from 96.85%, 95%, 85%, and 80%. In stage II patients, the 3-year OS for scores 0-4 were 88.6%, 76.5%, 90.5%, 65.5% and 60%. For stage III patients, 3-year OS for scores 0-6 were 70.9%, 68.3%, 64.1%, 50.9%, 38.4%, 18.5% and 5.2%. We also analyzed the mean survival of patients with different scores. For stage I patients, the mean OS was 55.980 months. In stage II, the mean OS was 51.550 months. The mean OS for stage III was 39.422 months. CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.
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Affiliation(s)
- Ai-Hua Sun
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Xin-Yu Zhang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Yang-Yang Huang
- Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Lei Chen
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Qing Wang
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Xiao-Cong Jiang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
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Lu L, Fang W, Yu J, Gao X, Wang X, Pan Y, Han W, Yan J, Xie H, Yao L, Yang J, Zheng J, Hong L, Li J, Li M, Shang L, Wu K, Ji G, Nie Y. Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study. Front Oncol 2024; 14:1327691. [PMID: 38444686 PMCID: PMC10912618 DOI: 10.3389/fonc.2024.1327691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/12/2024] [Indexed: 03/07/2024] Open
Abstract
Background Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.
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Affiliation(s)
- Linbin Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Wenzheng Fang
- Department of Oncology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Department of Oncology, the 900th Hospital of Joint Logistic Support Force, Chinese People's Liberation Army (PLA), Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Jun Yu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Xinlin Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Yan Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Weili Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Junya Yan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Huahong Xie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Liping Yao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Jianjun Yang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Jianyong Zheng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Liu Hong
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Jipeng Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Mengbin Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Lei Shang
- Department of Medical Statistics, School of Preventive Medicine, Fourth Military Medical University, Xi’an, China
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Gang Ji
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
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Lee JH, Kim DK, Lee MY, Lim HS, Kwon MJ, Lee YT, Yoon KJ, Park CH. The Association of Carbohydrate Antigen (CA) 19-9 Levels and Low Skeletal Muscle Mass in Healthy Adults. Nutrients 2023; 15:3394. [PMID: 37571330 PMCID: PMC10421491 DOI: 10.3390/nu15153394] [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: 06/19/2023] [Revised: 07/21/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a commonly used tumor marker for pancreatic cancer. However, CA 19-9 can be overexpressed in several benign inflammatory diseases. We investigated the relationship between high CA 19-9 level and low muscle mass (LMM) in healthy adults without cancer. Participants who underwent evaluation of muscle mass and CA 19-9 were included. Exclusion criteria were any malignancy, cardiovascular disease, tuberculosis, and chronic lung/liver disease. Participants were classified into "normal", "mild LMM", and "severe LMM" groups based on the skeletal muscle mass index. Multivariable logistic regression analyses were conducted to assess the association of high CA 19-9 with muscle mass status. A total of 263,061 adults were included. The mean age and SMI were 41.03 years and 7.13 kg/m2. After adjustments for various confounders, high CA 19-9 was independently associated with mild LMM (adjusted odds ratio, 1.677 [95% confidence interval, 1.533-1.834]) and severe LMM (2.651 [2.126-3.306]) compared to the normal group. Furthermore, the association between high CA 19-9 and severe LMM was stronger in men than in women. Elevated CA 19-9 levels were independently associated with a higher prevalence of LMM in healthy adults without cancer. Therefore, increased CA 19-9 could be utilized as a novel biomarker for sarcopenia.
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Affiliation(s)
- Jae Hyun Lee
- Department of Rehabilitation Medicine, Kosin University College of Medicine, Busan 49267, Republic of Korea;
- Department of Artificial Intelligence Convergence, Pukyong National University, Busan 48513, Republic of Korea
| | - Dong-Kun Kim
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (D.-K.K.); (H.-S.L.); (Y.-T.L.); (K.J.Y.)
| | - Mi-Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea;
| | - Han-Sol Lim
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (D.-K.K.); (H.-S.L.); (Y.-T.L.); (K.J.Y.)
| | - Min-Jung Kwon
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea;
| | - Yong-Taek Lee
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (D.-K.K.); (H.-S.L.); (Y.-T.L.); (K.J.Y.)
| | - Kyung Jae Yoon
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (D.-K.K.); (H.-S.L.); (Y.-T.L.); (K.J.Y.)
| | - Chul-Hyun Park
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea; (D.-K.K.); (H.-S.L.); (Y.-T.L.); (K.J.Y.)
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Prognostic impact of CEA/CA19-9 at the time of recurrence in patients with gastric cancer. Surg Today 2021; 51:1638-1648. [PMID: 33682011 DOI: 10.1007/s00595-021-02248-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/31/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE We evaluated the clinical impact of the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) values at the time of recurrence in gastric cancer patients. METHODS Among 790 patients with R0 resected gastric cancer without neoadjuvant therapy between 2004 and 2017, 89 recurrence cases were retrospectively evaluated. The clinical impact of CEA and CA19-9 values on recurrence sites and post-recurrent prognosis were evaluated using univariate and multivariate analyses. RESULTS The positive rates of CEA and CA19-9 at recurrence were significantly higher than the preoperative positive rates (CEA, 56% vs 24%; CA19-9, 37% vs 15%). Although CA19-9-positive patients at recurrence exhibited a poor survival, the difference was not significant. The positive rates of CEA at liver or lymph node recurrence were significantly higher than the preoperative positive rates. The positive rate of CA19-9 at peritoneal recurrence was significantly higher than the preoperative positive rate. CA19-9-positive patients at recurrence exhibited worse prognosis than CA19-9-negative patients, although the difference was not significant. At lymph node recurrence, CA19-9-positive patients exhibited a significantly worse survival than CA19-9-negative patients. CONCLUSION In recurrent gastric cancer, the positive status of CA19-9 at recurrence might have a negative prognostic impact after recurrence; particularly, in patients with lymph node recurrence.
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Jing A, Xu Q, Feng W, Liang G. An Electrochemical Immunosensor for Sensitive Detection of the Tumor Marker Carcinoembryonic Antigen (CEA) Based on Three-Dimensional Porous Nanoplatinum/Graphene. MICROMACHINES 2020; 11:mi11070660. [PMID: 32635249 PMCID: PMC7407820 DOI: 10.3390/mi11070660] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 06/30/2020] [Indexed: 12/18/2022]
Abstract
Carcinoembryonic antigen (CEA) is an important broad-spectrum tumor marker. The quantitative detection of a low concentration of CEA has important medical significance. In this study, three-dimensional porous graphene-oxide-supported platinum metal nanoparticles (3DPt/HGO) composites were prepared by a wet chemical method and modified on an electrode with enhanced conductivity, a large surface area, and good adsorption of immobilizing antibodies (Ab1). Horseradish peroxidase (HRP)-functionalized Au nanoparticles were fabricated to label the secondary antibodies (Ab2). The proposed immunosensor showed a good linear relationship in the range of 0.001–150 ng/mL for CEA and a detection limit of 0.0006 ng/mL. The immunosensor had high sensitivity, good stability and reproducibility, and has great application prospects for the clinical diagnosis of cancer.
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Affiliation(s)
- Aihua Jing
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (A.J.); (Q.X.); (W.F.)
| | - Qiong Xu
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (A.J.); (Q.X.); (W.F.)
| | - Wenpo Feng
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (A.J.); (Q.X.); (W.F.)
| | - Gaofeng Liang
- Medical College, Henan University of Science and Technology, Luoyang 471023, China
- Correspondence: ; Tel.: (+86)-0379-64162573
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Wu P, Wang J. Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy. Oncol Lett 2019; 18:1733-1744. [PMID: 31423240 PMCID: PMC6607250 DOI: 10.3892/ol.2019.10505] [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: 08/23/2018] [Accepted: 05/14/2019] [Indexed: 11/14/2022] Open
Abstract
The clinical effect of interventional therapy on gastric cancer after chemotherapy and effect on inflammatory factors in peripheral blood serum of patients were investigated. A retrospective analysis of 429 patients with gastric cancer treated in Xiangyang No. 1 People's Hospital, Hubei University of Medicine from July 2008 to December 2014 was performed. Among them, 220 patients received interventional therapy after chemotherapy as the experimental group, and 209 patients received conventional therapy as the control group. Serum carcinoembryonic antigen (CEA), tumor markers CA19-9, interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) levels were measured before and after chemotherapy. The correlation between the concentration of CEA and CA19-9 before and after treatment and the levels of IL-6, IL-8 and IL-10 were analyzed in the experimental group, and all patients were followed up for 3 years. There were no significant differences in CEA, CA19-9, IL-6, IL-8 and IL-10 between the two groups before chemotherapy (P>0.05). After treatment, the concentrations of CEA, CA19-9, IL-6, IL-8 and IL-10 in the experimental group were significantly lower than those in the control group before and after treatment (P<0.05). The clinical efficacy and adverse reactions of the experimental group were significantly better than those in the control group (P<0.05). Pearson's correlation analysis showed that the concentrations of CEA and CA19-9 in the serum of the experimental group before and after treatment were positively correlated with the levels of IL-6, IL-8 and IL-10 (P<0.05). The 3-year overall survival rate of the study group was significantly higher than that of the control group (P<0.05). Cox regression analysis showed that age, Borrmann classification, degree of differentiation, and history of Helicobacter pylori infection were independent prognostic factors for patients with gastric cancer. Compared with traditional treatment, interventional therapy can greatly improve the recovery of gastric cancer patients after chemotherapy, reduce the occurrence of complications and inflammation, and improve the survival rate of patients.
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Affiliation(s)
- Puzhao Wu
- Department of Interventional Oncology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Jing Wang
- Department of Oncology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
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Lu R, Shao Y, Tao X, Ye G, Xiao B, Guo J. Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues. J Clin Lab Anal 2019; 33:e22984. [PMID: 31328820 PMCID: PMC6868420 DOI: 10.1002/jcla.22984] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 06/29/2019] [Accepted: 07/02/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are a special class of endogenous noncoding RNAs that have numerous biological functions in normal situation and diseases including cancers. However, the clinical significance of circRNAs in gastric cancer (GC) remains largely unknown. Here, we chose two representative circRNAs, hsa_circ_0067582 and hsa_circ_0005758, to investigate their clinical significance in GC patients. METHODS Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we explored the expression levels of hsa_circ_0067582 and hsa_circ_0005758 in tissues with different stages of gastric tumorigenesis. Then, the relationships between their expression levels and GC patients' clinicopathological factors were further investigated. Receiver operating characteristic (ROC) curves were established for evaluating diagnostic values of hsa_circ_0067582 and hsa_circ_0005758. RESULTS Compared with healthy control tissues, both hsa_circ_0067582 and hsa_circ_0005758 were significantly decreased in GC tissues. Besides, hsa_circ_0067582 expression was associated with GC patients' tissue CEA level (P <.001) and stages (P = .037); and hsa_circ_0005758 expression was relevant to tissue CEA level (P < .001) and perineural invasion (P = .048). The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.671. The cutoff value was set at 10.61, with which the sensitivity and specificity were 55.2% and 75.0%, respectively. Similar to hsa_circ_0005758, the AUC of hsa_circ_0005758 was 0.721. The cutoff value was set at 10.20, with which the sensitivity and specificity were 75.0% and 67.7%, respectively. CONCLUSION These results showed that both hsa_circ_0067582 and hsa_circ_0005758 may play an important role in gastric carcinogenesis; and they may be potential indicators for GC diagnosis.
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Affiliation(s)
- Rongdan Lu
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Yongfu Shao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Xueping Tao
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.,Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Guoliang Ye
- Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
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Qiao YF, Chen CG, Yue J, Ma MQ, Ma Z, Yu ZT. Prognostic significance of preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of patients with gastric cardia cancer. World J Gastroenterol 2017; 23:1424-1433. [PMID: 28293089 PMCID: PMC5330827 DOI: 10.3748/wjg.v23.i8.1424] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 12/16/2016] [Accepted: 01/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA levels in peripheral blood of patients with gastric cardia cancer (GCC).
METHODS We detected the preoperative and postoperative mRNA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.
RESULTS Elevated preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 mRNA, and preoperative and postoperative CEA mRNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status (P = 0.018), preoperative CK19 (P = 0.035) and CEA (P = 0.011) mRNA levels were independent prognostic factors for overall survival (OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively (P < 0.001).
CONCLUSION Elevated preoperative CK19 and CEA mRNA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.
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Yan X, Wang K, Lu W, Qin W, Cui D, He J. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4. NANOSCALE RESEARCH LETTERS 2016; 11:138. [PMID: 26969591 PMCID: PMC4788655 DOI: 10.1186/s11671-016-1355-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 03/03/2016] [Indexed: 05/29/2023]
Abstract
Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal antibodies (mAbs) against CA72-4 were employed. One of them was coated as a test line, while another mAb was labeled with quantum dots and coated onto conjugate pad. The goat anti-mouse IgG was immobilized as a control line. After sample was added, a sandwich structure was formed with CA72-4 and these two mAbs. The fluorescent signal from quantum dots (QD)-labeled mAb in sandwich structure was related to the amount of detected CA72-4. A CCD-based reader was used to realize quantitative detection of CA72-4. Results showed that developed QD-labeled lateral flow strips to detect CA72-4 biomarker with the sensitivity of 2 IU/mL and 10 min detection time. One hundred sera samples from clinical patients with gastric cancer and healthy people were used to confirm specificity of this strip method; results showed that established strip method own 100 % reproducibility and 100 % specificity compared with Roche electrochemiluminescence assay results. In conclusion, CdSe/ZnS quantum dot-labeled lateral flow strips for detection of CA72-4 could realize rapid, sensitive, and specific detection of clinical samples and could own great potential in clinical translation in near future.
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Affiliation(s)
- Xinyu Yan
- />Out-Patient Department, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, 510280 Guangzhou, Guangdong People’s Republic of China
| | - Kan Wang
- />Institute of Nano Biomedical and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, People’s Republic of China
- />National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, People’s Republic of China
| | - Wenting Lu
- />Out-Patient Department, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, 510280 Guangzhou, Guangdong People’s Republic of China
| | - Weijian Qin
- />Institute of Nano Biomedical and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, People’s Republic of China
| | - Daxiang Cui
- />Institute of Nano Biomedical and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, People’s Republic of China
- />National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, People’s Republic of China
| | - Jinghua He
- />Out-Patient Department, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, 510280 Guangzhou, Guangdong People’s Republic of China
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Palliative Gastrectomy Prolongs Survival of Metastatic Gastric Cancer Patients with Normal Preoperative CEA or CA19-9 Values: A Retrospective Cohort Study. Gastroenterol Res Pract 2016; 2016:6846027. [PMID: 27990157 PMCID: PMC5136406 DOI: 10.1155/2016/6846027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 09/18/2016] [Indexed: 12/27/2022] Open
Abstract
Background. Palliative gastrectomy has been suggested to improve survival of patients with metastatic gastric cancer, but limitations in study design and availability of robust prognostic factors have cast doubt on the overall merit of this procedure. Methods. The characteristics and clinical outcomes of 173 patients diagnosed between 2008 and 2012 were analyzed to determine the value of palliative gastrectomy and to identify potential prognostic factors. Results. Median overall patient survival was 6.5 months. To attenuate potential selection bias, patients with adequate performance and survival time of ≥ 2 months since diagnosis were included for risk factor analysis (n = 137). The median overall survival was longer for patients who were younger than 60 years, had better performance status (8.7 versus 6.4 months, P = 0.015), received systemic chemotherapy, or had palliative gastrectomy in univariate analyses. Gastrectomy (P = 0.002) remained statistically significant in multivariate analyses. Subgroup analysis showed that patients aged < 60 years, CEA < 5 ng/mL or CA19-9 < 35 U/mL, obtained a survival advantage from palliative gastrectomy. In fact, palliative gastrectomy doubled overall survival for patients who had normal CEA and/or normal CA19-9. Conclusions. Palliative gastrectomy prolongs the survival of metastatic gastric cancer patients with normal CEA and/or CA19-9 level at the time of diagnosis.
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11
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Dang Y, Ouyang X, Wang K, Zhang F, Huang Q. Evaluation of the Clinical Significance of Serum Carcinoembryonic Antigen in Patients with Resectable Gastric Adenocarcinoma. Arch Med Res 2016; 47:196-9. [PMID: 27387021 DOI: 10.1016/j.arcmed.2016.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 06/24/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Carcinoembryonic antigen (CEA) is the most commonly used tumor marker for gastrointestinal cancers but its value for resectable gastric adenocarcinoma (RGA) patients in areas of high GA incidence is uncertain. METHODS We retrospectively studied 400 subjects with RGA from the Fujian Province in China, which has a high incidence of GA. Patients had surgery between January 2010 and December 2013. CEA was measured and correlated to pathology. RESULTS High pretreatment serum CEA (>5 ng/mL) was associated with patient age (p = 0.000), tumor size (p = 0.008), and T and N stages (p = 0.002, p = 0.032, respectively), alpha fetoprotein (p = 0.014), and CA19-9 (p = 0.000). High CEA was significantly associated with poor overall survival. Overall survival in the whole group of patients was 63.8%, whereas it was only 42.9% in the high CEA group (p = 0.0001). Mean overall survival for high CEA patients was significantly shorter than patients with low CEA (36.5 ± 2.63 months vs. 47.4 ± 0.98 months, p = 0.000). Multivariate analysis confirmed that pretreatment serum CEA was an independent prognostic factor for increased death risk. Additionally, mean CEA in 45 high CEA patients was reduced after surgery. CONCLUSIONS Pretreatment serum CEA may help to predict survival for patients with RGA in high GA incidence areas.
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Affiliation(s)
- Yuan Dang
- Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Fuzhou City, Fujian Province 350025, China
| | - Xiaojuan Ouyang
- Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Fuzhou City, Fujian Province 350025, China
| | - Kai Wang
- Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Fuzhou City, Fujian Province 350025, China
| | - Fan Zhang
- Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Fuzhou City, Fujian Province 350025, China
| | - Qiaojia Huang
- Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Fuzhou City, Fujian Province 350025, China.
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Inagaki Y, Song P, Tang W, Kokudo N. Cancer-associated carbohydrate antigens for clinical diagnostic markers--its effectiveness and limitations. Drug Discov Ther 2015; 9:129-32. [PMID: 25994064 DOI: 10.5582/ddt.2015.01031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Cancer cells express various aberrant glycoconjugates. Several kinds of carbohydrate antigens have been used for the serological tumor markers. In particular, the serological level of sialylated carbohydrate antigens, which contain the sialic acid residue in their structure, showed effectiveness in diagnosing cancer behavior. Although large number of carbohydrate antigens in serum of cancer patients was elevated broadly in various cancers, each tumor marker has different sensitivity and specificity for each cancer. Therefore, the combined use of several tumor markers which have different characteristics is effective for better sensitivity in diagnosing cancer behavior. The mechanism of synthesizing cancer-associated carbohydrate antigens is not fully understood because it is very complex. In addition, new cancer-associated carbohydrate antigens are also identified by molecular oncological studies. Those investigations are considered to develop more effective tumor markers to diagnose cancer behavior.
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Affiliation(s)
- Yoshinori Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
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Fernandes E, Ferreira JA, Andreia P, Luís L, Barroso S, Sarmento B, Santos LL. New trends in guided nanotherapies for digestive cancers: A systematic review. J Control Release 2015; 209:288-307. [PMID: 25957905 DOI: 10.1016/j.jconrel.2015.05.003] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 05/02/2015] [Accepted: 05/05/2015] [Indexed: 02/06/2023]
Abstract
Digestive tract tumors are among the most common and deadliest malignancies worldwide, mainly due to late diagnosis and lack of efficient therapeutics. Current treatments essentially rely on surgery associated with (neo)adjuvant chemotherapy agents. Despite an upfront response, conventional drugs often fail to eliminate highly aggressive clones endowed with chemoresistant properties, which are responsible for tumor recurrence and disease dissemination. Synthetic drugs also present severe adverse systemic effects, hampering the administration of biologically effective dosages. Nanoencapsulation of chemotherapeutic agents within biocompatible polymeric or lipid matrices holds great potential to improve the pharmacokinetics and efficacy of conventional chemotherapy while reducing systemic toxicity. Tagging nanoparticle surfaces with specific ligands for cancer cells, namely monoclonal antibodies or antibody fragments, has provided means to target more aggressive clones, further improving the selectivity and efficacy of nanodelivery vehicles. In fact, over the past twenty years, significant research has translated into a wide array of guided nanoparticles, providing the molecular background for a new generation of intelligent and more effective anti-cancer agents. Attempting to bring awareness among the medical community to emerging targeted nanopharmaceuticals and foster advances in the field, we have conducted a systematic review about this matter. Emphasis was set on ongoing preclinical and clinical trials for liver, colorectal, gastric and pancreatic cancers. To the best of our knowledge this is the first systematic and integrated overview on this field. Using a specific query, 433 abstracts were gathered and narrowed to 47 manuscripts when matched against inclusion/exclusion criteria. All studies showed that active targeting improves the effectiveness of the nanodrugs alone, while lowering its side effects. The main focus has been on hepatocarcinomas, mainly by exploring glycans as homing molecules. Other ligands such as peptides/small proteins and antibodies/antibody fragments, with affinity to either tumor vasculature or tumor cells, have also been widely and successfully applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few solutions have been presented for pancreatic tumors. To this date only three nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine-functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid tumors; and iii) MBP-426, a transferrin-liposome-oxaliplatin conjugate, also for advanced stage tumors. Still, none has been approved for clinical use. However, based on the high amount of pre-clinical studies showing enthusiastic results, the number of clinical trials is expected to increase in the near future. A more profound understanding about the molecular nature of chemoresistant clones and cancer stem cell biology will also contribute to boost the field of guided nanopharmacology towards more effective solutions.
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Affiliation(s)
- Elisabete Fernandes
- Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal; I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal and INEB - Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
| | - José Alexandre Ferreira
- Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal; Mass Spectrometry Center, QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
| | - Peixoto Andreia
- Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal
| | - Lima Luís
- Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal; Nucleo de Investigação em Farmácia - Centro de Investigação em Saúde e Ambiente (CISA), Health School of the Polytechnic Institute of Porto, Porto, Portugal
| | - Sérgio Barroso
- Serviço de Oncologia, Hospital de Évora, Évora, Portugal
| | - Bruno Sarmento
- I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal and INEB - Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra PRD, Portugal
| | - Lúcio Lara Santos
- Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal; Health School of University of Fernando Pessoa, Porto, Portugal; Department of Surgical Oncology, Portuguese Institute of Oncology, Porto, Portugal
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