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Yang J, Li ZX, Song MJ, Han SJ, Yang AJ, Zhang ZP, Sui CS, Qiao JL, Huang WH, He JQ. Prognostic value and therapeutic efficacy of interstitial circulating tumor cells in patients with advanced gastric cancer. World J Clin Oncol 2025; 16:101762. [DOI: 10.5306/wjco.v16.i5.101762] [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: 09/25/2024] [Revised: 03/08/2025] [Accepted: 04/08/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer (GC) patients. To optimize treatment stratification and management, there is an urgent need for efficient and non-invasive biomarkers. A meta-analysis on the prognostic role of circulating tumor cells (CTCs) in GC revealed a strong association between CTCs and patient prognosis. Among CTC subtypes, Interstitial CTCs (I-CTCs) exhibited the strongest invasiveness. This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.
AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC. To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients. To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.
METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020. The expression levels of I-CTCs were measured, and patient survival was monitored. The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels. Based on this cut-off value, 59 GC patients were grouped into positive and negative groups. The differences in clinicopathological characteristics between the two groups were analyzed. Patient survival was follow-up and recorded until October 2022. Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors. The Kaplan-Meier method and Cox regression model were used, respectively.
RESULTS A total of 59 patients were included in this study, and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5, with an area under the curve of 0.8356 (95%CI: 0.7122-0.9590). The I-CTC count of ≥ 5 defines the positive group, while counts < 5 are classified as the negative group. Positive I-CTCs correlated with the degree of tumor differentiation and disease progression (P < 0.05). 16 of 59 patients received neoadjuvant chemotherapy. There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy. Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group (P < 0.05). Multifactorial analysis revealed that I-CTCs positivity (HR = 13.323, 95%CI: 1.675-105.962, P = 0.014) was an independent risk factor for survival in patients with advanced GC.
CONCLUSION In patients with advanced GC, an I-CTC count of ≥ 5 is associated with both poor prognosis and reduced chemotherapy efficacy. I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
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Affiliation(s)
- Jing Yang
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
| | - Zu-Xi Li
- Department of Peripheral Vascular Intervention, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730060, Gansu Province, China
| | - Mei-Juan Song
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Shang-Jun Han
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ai-Jia Yang
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ze-Ping Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Chang-Sheng Sui
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ji-Lin Qiao
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wen-Hua Huang
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
| | - Jun-Qiang He
- Department of General Surgery, Xinhui People’s Hospital of Southern Medical University, Jiangmen 529000, Guangdong Province, China
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Wang C, Li J, Luo T, Zhu S, Zhao M, Jia Y, Liu Y. Detection of circulating tumor cells that predicts the efficacy of neoadjuvant chemotherapy for locally advanced triple-negative breast cancer. Front Med (Lausanne) 2025; 12:1536971. [PMID: 40370743 PMCID: PMC12075245 DOI: 10.3389/fmed.2025.1536971] [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: 11/29/2024] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
Objective This study aims to assess the predictive potential of circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) in locally advanced triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC) compared to the RECIST 1.1 standard. Methods We analyzed 112 patients with TNBC at the Liaoning Tumor Hospital. CTCs and CTSCs were evaluated before NAC, on the first NAC cycle day, and after NAC. We assessed the ability of positive CTSCs after the first cycle to predict NAC resistance (requiring regimen change) with a 91% specificity. Additionally, we analyzed CTC dynamics during the first NAC cycle to predict efficacy (often reaching MP4 or MP5) with 87% sensitivity and 80% specificity. Results Positive CTSCs post-first cycle predicted NAC resistance with high specificity (91%). The gradual decline in CTCs during the first NAC cycle indicated NAC efficacy, allowing the regimen to continue with a sensitivity of 87% and specificity of 80%. Conclusion This study suggests that positive CTSCs after the first NAC cycle predict resistance, thereby facilitating early detection (≥ 6 weeks earlier than RECIST). Gradual CTC reduction during the first cycle predicts efficacy, enabling regimen continuation. CTCs and CTSCs show promise as predictive markers for NAC efficacy in patients with locally advanced TNBC.
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Affiliation(s)
| | | | | | | | | | | | - Yefu Liu
- Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Dalian Medical University, Shenyang, China
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Choi H, Hwang W. Anesthetic Approaches and Their Impact on Cancer Recurrence and Metastasis: A Comprehensive Review. Cancers (Basel) 2024; 16:4269. [PMID: 39766169 PMCID: PMC11674873 DOI: 10.3390/cancers16244269] [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: 10/21/2024] [Revised: 11/10/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
Cancer recurrence and metastasis remain critical challenges following surgical resection, influenced by complex perioperative mechanisms. This review explores how surgical stress triggers systemic changes, such as neuroendocrine responses, immune suppression, and inflammation, which promote the dissemination of residual cancer cells and circulating tumor cells. Key mechanisms, such as epithelial-mesenchymal transition and angiogenesis, further enhance metastasis, while hypoxia-inducible factors and inflammatory responses create a microenvironment conducive to tumor progression. Anesthetic agents and techniques modulate these mechanisms in distinct ways. Inhaled anesthetics, such as sevoflurane, may suppress immune function by increasing catecholamines and cytokines, thereby promoting cancer progression. In contrast, propofol-based total intravenous anesthesia mitigates stress responses and preserves natural killer cell activity, supporting immune function. Opioids suppress immune surveillance and promote angiogenesis through the activation of the mu-opioid receptor. Opioid-sparing strategies using NSAIDs show potential in preserving immune function and reducing recurrence risk. Regional anesthesia offers benefits by reducing systemic stress and immune suppression, though the clinical outcomes remain inconsistent. Additionally, dexmedetomidine and ketamine exhibit dual effects, both enhancing and inhibiting tumor progression depending on the dosage and context. This review emphasizes the importance of individualized anesthetic strategies to optimize long-term cancer outcomes. While retrospective studies suggest potential benefits of propofol-based total intravenous anesthesia and regional anesthesia, further large-scale trials are essential to establish the definitive role of anesthetic management in cancer recurrence and survival.
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Affiliation(s)
| | - Wonjung Hwang
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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Huh J, Hwang W. The Role of Anesthetic Management in Lung Cancer Recurrence and Metastasis: A Comprehensive Review. J Clin Med 2024; 13:6681. [PMID: 39597826 PMCID: PMC11594908 DOI: 10.3390/jcm13226681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 10/31/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
Lung cancer remains a leading cause of cancer-related mortality worldwide. Although surgical treatment is a primary approach, residual cancer cells and surgery-induced pathophysiological changes may promote cancer recurrence and metastasis. Anesthetic agents and techniques have recently been shown to potentially impact these processes by modulating surgical stress responses, immune function, inflammatory pathways, and the tumor microenvironment. Anesthetics can influence immune-modulating cytokines, induce pro-inflammatory factors such as HIF-1α, and alter natural-killer cell activity, affecting cancer cell survival and spread. Preclinical studies suggest volatile anesthetics may promote tumor progression by triggering pro-inflammatory signaling, while propofol shows potential antitumor properties through immune-preserving effects and reductions in IL-6 and other inflammatory markers. Additionally, opioids are known to suppress immune responses and stimulate pathways that may support cancer cell proliferation, whereas regional anesthesia may reduce these risks by decreasing the need for systemic opioids and volatile agents. Despite these findings, clinical data remain inconclusive, with studies showing mixed outcomes across patient populations. Current clinical trials, including comparisons of volatile agents with propofol-based total intravenous anesthesia, aim to provide clarity but highlight the need for further investigation. Large-scale, well-designed studies are essential to validate the true impact of anesthetic choice on cancer recurrence and to optimize perioperative strategies that support long-term oncologic outcomes for lung cancer patients.
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Affiliation(s)
| | - Wonjung Hwang
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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Senchukova MA. Colorectal cancer and dormant metastases: Put to sleep or destroy? World J Gastrointest Oncol 2024; 16:2304-2317. [PMID: 38994146 PMCID: PMC11236221 DOI: 10.4251/wjgo.v16.i6.2304] [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: 02/24/2024] [Revised: 04/19/2024] [Accepted: 04/30/2024] [Indexed: 06/13/2024] Open
Abstract
After reading the review by An et al "Biological factors driving colorectal cancer metastasis", which covers the problem of the metastasis of colorectal cancer (CRC), I had a desire to discuss with readers one of the exciting problems associated with dormant metastases. Most deaths from CRCs are caused by metastases, which can be detected both at diagnosis of the primary tumor and several years or even decades after treatment. This is because tumor cells that enter the bloodstream can be destroyed by the immune system, cause metastatic growth, or remain dormant for a long time. Dormant tumor cells may not manifest themselves throughout a person's life or, after some time and under appropriate conditions, may give rise to the growth of metastases. In this editorial, we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation, as well as factors that contribute to the activation of dormant metastases in CRCs. We will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
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Eskandarion MR, Eskandarieh S, Tutunchi S, Shakoori Farahani A, Shirkoohi R. Investigating the role of circulating tumor cells in gastric cancer: a comprehensive systematic review and meta-analysis. Clin Exp Med 2024; 24:59. [PMID: 38554188 PMCID: PMC10981629 DOI: 10.1007/s10238-024-01310-6] [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: 07/13/2023] [Accepted: 02/19/2024] [Indexed: 04/01/2024]
Abstract
Investigating the role of circulating tumor cells (CTCs) and their characteristics is still controversial in patients with gastric cancer (GC). Therefore, in this study, to provide a comprehensive review and meta-analyses of the literature on association of CTCs with gastric cancer, Scopus, Web of Science, Embase, and Medline were searched for systematic reviews and meta-analyses conducted during February 2022 using the keywords. Risk of bias, hazard ratios (HRs), and risk differences (RD) were assessed. Forty-five studies containing 3,342 GC patients from nine countries were assessed. The overall prevalence of CTC in GC was 69.37% (60.27, 77.78). The pooled result showed that increased mortality in GC patients was significantly associated with positive CTCs, poor overall survival (HR = 2.73, 95%CI 2.34-3.24, p < 0.001), and progression-free survival rate (HR = 2.78, 95%CI 2.01-3.85, p < 0.001). Subgroup analyses regarding markers, detection methods, treatment type, presence of distance metastasis, presence of lymph node metastasis, and overall risk of bias showed significant associations between the groups in terms of the incidence rates of CTCs, OS, and PFS. In addition, the results of risk differences based on sampling time showed that the use of the cell search method (RD: - 0.19, 95%CI (- 0.28, - 0.10), p < 0.001), epithelial marker (RD: - 0.12, 95%CI (- 0.25, 0.00), p 0.05) and mesenchymal markers (RD: - 0.35, 95%CI (- 0.57, - 0.13), p 0.002) before the treatment might have a higher diagnostic power to identify CTCs and also chemotherapy treatment (RD: - 0.17, 95%CI (- 0.31, - 0.03), p 0.016) could significantly reduce the number of CTCs after the treatment. We also found that the risk differences between the clinical early and advanced stages were not statistically significant (RD: - 0.10, 95%CI (- 0.23, 0.02), P 0.105). Also, in the Lauren classification, the incidence of CTC in the diffuse type (RD: - 0.19, 95%CI (- 0.37, - 0.01), P0.045) was higher than that in the intestinal type. Meta-regression analysis showed that baseline characteristics were not associated with the detection of CTCs in GC patients. According to our systematic review and meta-analysis, CTCs identification may be suggested as a diagnostic technique for gastric cancer screening, and the outcomes of CTC detection may also be utilized in the future to create personalized medicine programs.
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Affiliation(s)
| | - Sharareh Eskandarieh
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Tutunchi
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Shakoori Farahani
- Medical Genetics Ward, IKHC Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Research Center, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran.
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Xia F, Zhang Q, Ndhlovu E, Zhang M, Zou Y. A Novel Nomogram to Predict Resectable Gastric Cancer Based on Preoperative Circulating Tumor Cell. Clin Transl Gastroenterol 2024; 15:e00561. [PMID: 36727697 PMCID: PMC10887436 DOI: 10.14309/ctg.0000000000000561] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 11/21/2022] [Indexed: 02/03/2023] Open
Abstract
INTRODUCTION Circulating tumor cells (CTCs) have been suggested to have an important prognostic role in gastrointestinal tumors. We developed a preoperative CTC-based nomogram to predict the prognosis of patients with resectable gastric cancer after surgery and established a risk stratification system based on the nomogram. METHODS From January 2012 to June 2017, we screened 258 patients with gastric cancer treated with surgery from one center as the training cohort and 133 patients with gastric cancer treated with surgery from another as the validation cohort, screened prognostic factors for the training cohort using univariate and multivariate Cox risk proportional models, created predictive overall survival (OS) and a recurrence-free survival (RFS) nomogram, and plotted the receiver operating characteristic curve and calibration curve for this nomogram in the training and validation cohorts. Risk score stratification was performed according to the nomogram, and OS curves were plotted for the low, medium, and high-risk groups using the Kaplan-Meier method. RESULTS The CTC positivity rate was 78.5% in all patients. CTC, TNM stage, and Ki-67 were the prognostic factors affecting OS and RFS after gastric cancer surgery. The nomogram consisted of these 3 variables. In the training group, the area under the curve of the nomogram for OS at 1, 3, and 5 years was 0.918, 0.829, and 0.813, respectively, and the area under the curve for RFS was 0.900, 0884, and 0.839, respectively. There was a statistically significant difference in OS among the low, medium, and high-risk groups according to the risk stratification system constructed from nomogram scores ( P < 0.001). DISCUSSION Two nomograms based on preoperative CTC were established to predict OS and RFS after resectable gastric cancer. The 2 nomograms had good discrimination and calibration and significant stratification ability of the risk stratification system established according to them.
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Affiliation(s)
- Feng Xia
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qiao Zhang
- Zhongshan People's Hospital Affiliated to Guangdong Medical University, Guangdong, China
| | - Elijah Ndhlovu
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mingyu Zhang
- Department of Digestive Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - You Zou
- Gastrointestinal Surgery Center, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
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Deng Q, Jiang B, Yan H, Wu J, Cao Z. Circulating tumor cells in gastric cancer: developments and clinical applications. Clin Exp Med 2023; 23:4385-4399. [PMID: 37548815 DOI: 10.1007/s10238-023-01158-2] [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: 02/16/2023] [Accepted: 07/24/2023] [Indexed: 08/08/2023]
Abstract
Circulating tumor cells (CTCs), which are shed from primary tumor or metastatic sites into the bloodstream and subsequently seed into distant tissues, are considered as the precursors of metastases. Gastric cancer (GC) is a highly heterogeneous malignant tumor. With regard to the diagnosis of GC, secondary pathological biopsy is difficult, while invasive examination is harmful to patients. In recent years, CTCs have made great progress in tumor diagnosis, prognosis prediction, efficacy detection and treatment guidance, but the research on the role of CTCs in GC remains limited. The following sections review the landmark studies demonstrating the technical approaches of CTCs monitoring in the field of GC. Moreover, we highlight the clinical application of CTCs numbers and phenotypes in monitoring the therapeutic efficacy and judging patient prognosis by sequential blood analyses.
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Affiliation(s)
- Qian Deng
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Bo Jiang
- Department of Thoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Haijiao Yan
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Zhenzhen Cao
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
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Jin T, Liang PP, Chen ZH, He FJ, Li ZD, Chen ZW, Hu JK, Yang K. Association between circulating tumor cells in the peripheral blood and the prognosis of gastric cancer patients: a meta-analysis. Ther Adv Med Oncol 2023; 15:17588359231183678. [PMID: 37435560 PMCID: PMC10331349 DOI: 10.1177/17588359231183678] [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: 12/02/2022] [Accepted: 05/31/2023] [Indexed: 07/13/2023] Open
Abstract
Background Research on the correlation between circulating tumor cells (CTCs) and gastric cancer (GC) has increased rapidly in recent years. However, whether CTCs are associated with GC patient prognosis is highly controversial. Objective This study aims to evaluate the value of CTCs to predict the prognosis of GC patients. Design A meta-analysis. Data Sources and Methods We searched the PubMed, Embase, and Cochrane Library databases for studies that reported the prognostic value of CTCs in GC patients before October 2022. The association between CTCs and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) and progression-free survival (PFS) of GC patients was assessed. Subgroup analyses were stratified by sampling times (pre-treatment and post-treatment), detection targets, detection method, treatment method, tumor stage, region, and HR (Hazard Ratio) extraction methods. Sensitivity analysis was performed by removing individual studies to assess the stability of the results. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. Results We initially screened 2000 studies, of which 28 were available for further analysis, involving 2383 GC patients. The pooled analysis concluded that the detection of CTCs was associated with poor OS (HR = 1.933, 95% CI 1.657-2.256, p < 0.001), DFS/RFS (HR = 3.228, 95% CI 2.475-4.211, p < 0.001), and PFS (HR = 3.272, 95% CI 1.970-5.435, p < 0.001). Furthermore, the subgroup analysis stratified by tumor stage (p < 0.01), HR extraction methods (p < 0.001), detection targets (p < 0.001), detection method (p < 0.001), sampling times (p < 0.001), and treatment method (p < 0.001) all showed that CTC detection was associated with poor OS and DFS/RFS for GC patients. Furthermore, the study showed that CTCs were associated with the poor DFS/RFS of GC when CTCs were detected for patients from Asian or No-Asian regions (p < 0.05). In addition, higher CTCs predicted poorer OS for GC patients who are from Asian regions (p < 0.001), but without statistical difference for GC patients from No-Asian regions (p = 0.490). Conclusion CTC detection in peripheral blood was associated with poor OS, DFS/RFS, and PFS in patients with GC.
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Affiliation(s)
- Tao Jin
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Pan-Ping Liang
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ze-Hua Chen
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Feng-Jun He
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ze-Dong Li
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zheng-Wen Chen
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian-Kun Hu
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Kun Yang
- Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Asawa S, Nüesch M, Gvozdenovic A, Aceto N. Circulating tumour cells in gastrointestinal cancers: food for thought? Br J Cancer 2023; 128:1981-1990. [PMID: 36932192 DOI: 10.1038/s41416-023-02228-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/17/2023] [Accepted: 03/02/2023] [Indexed: 03/19/2023] Open
Abstract
Gastrointestinal (GI) cancers account for 35% of cancer-related deaths, predominantly due to their ability to spread and generate drug-tolerant metastases. Arising from different locations in the GI system, the majority of metastatic GI malignancies colonise the liver and the lungs. In this context, circulating tumour cells (CTCs) are playing a critical role in the formation of new metastases, and their presence in the blood of patients has been correlated with a poor outcome. In addition to their prognostic utility, prospective targeting of CTCs may represent a novel, yet ambitious strategy in the fight against metastasis. A better understanding of CTC biology, mechanistic underpinnings and weaknesses may facilitate the development of previously underappreciated anti-metastasis approaches. Here, along with related clinical studies, we outline a selection of the literature describing biological features of CTCs with an impact on their metastasis forming ability in different GI cancers.
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Affiliation(s)
- Simran Asawa
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Manuel Nüesch
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Ana Gvozdenovic
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Nicola Aceto
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland.
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Schoenberg MB, Han Y, Li X, Li X, Bucher JN, Börner N, Koch D, Guba MO, Werner J, Bazhin AV. Dynamics of Peripheral Blood Immune Cells during the Perioperative Period after Digestive System Resections: A Systematic Analysis of the Literature. J Clin Med 2023; 12:jcm12020718. [PMID: 36675647 PMCID: PMC9866033 DOI: 10.3390/jcm12020718] [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: 10/02/2022] [Revised: 11/22/2022] [Accepted: 01/11/2023] [Indexed: 01/18/2023] Open
Abstract
An operation in itself is a kind of trauma and may lead to immunosuppression followed by a bounce back. Not many studies exist that describe dynamics of the distribution of peripheral blood (PB) immune cells during the perioperative period. Considering this scarcity, we aggregated the data on the dynamics of immune cells in patients with digestive system resections during the perioperative period and the relationship with short- and long-term prognoses. By the systematic retrieval of documents, we collected perioperative period data on white blood cells (WBC), lymphocytes, neutrophil-lymphocyte ratio (NLR), CD4+ T cells, CD8+ T cells, helper T cells (Th), B cells, natural killer cells (NK), dendritic cells (DCs), regulatory T cells (Tregs), regulatory B cells (Bregs), and Myeloid derived suppressor cells (MDSC). The frequency and distribution of these immune cells and the relationship with the patient's prognosis were summarized. A total of 1916 patients' data were included. Compared with before surgery, WBC, lymphocytes, CD4+ cells, CD8+ T cells, MDSC, and NK cells decreased after surgery, and then returned to preoperative levels. After operation DCs increased, then gradually recovered to the preoperative level. No significant changes were found in B cell levels during the perioperative period. Compared with the preoperative time-point, Tregs and Bregs both increased postoperatively. Only high levels of the preoperative and/or postoperative NLR were found to be related to the patient's prognosis. In summary, the surgery itself can cause changes in peripheral blood immune cells, which might change the immunogenicity. Therefore, the immunosuppression caused by the surgical trauma should be minimized. In oncological patients this might even influence long-term results.
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Affiliation(s)
- Markus Bo Schoenberg
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
- Medical Center Gollierplatz, 80339 Munich, Germany
| | - Yongsheng Han
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Xiaokang Li
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Xinyu Li
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Julian Nikolaus Bucher
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Nikolaus Börner
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Dominik Koch
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Markus Otto Guba
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
- Transplantation Center Munich, Hospital of the LMU, Campus Grosshadern, 81377 Munich, Germany
| | - Jens Werner
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Alexandr V. Bazhin
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
- Correspondence: ; Tel.: +49-89-4400-0
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12
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Ullah A, Ullah N, Nawaz T, Aziz T. Molecular Mechanisms of Sanguinarine in Cancer Prevention and Treatment. Anticancer Agents Med Chem 2023; 23:765-778. [PMID: 36045531 DOI: 10.2174/1871520622666220831124321] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 07/08/2022] [Accepted: 07/19/2022] [Indexed: 11/22/2022]
Abstract
Historically, natural plant-derived drugs received a great impact of consideration in the treatment of several human-associated disorders. Cancer is a devastating disease and the second most cause of mortality. Sanguinarine (SANG), a naturally isolated plant alkaloidal agent, possesses chemo-preventive effects. Several studies have revealed that SANG impedes tumor metastasis and development by disrupting a wide range of cell signaling pathways and its molecular targets, such as BCL-2, MAPKs, Akt, NF-κB, ROS, and microRNAs (miRNAs). However, its low chemical stability and poor oral bioavailability remain key issues in its use as a medicinal molecule. A novel method (e.g., liposomes, nanoparticles, and micelles) and alternative analogs provide an exciting approach to alleviate these problems and broaden its pharmacokinetic profile. Cancer-specific miRNA expression is synchronized by SANG, which has also been uncertain. In this critical study, we review the utilization of SANG mimics and nano-technologies to improve its support in cancer. We focus on recently disclosed studies on SANG anti-cancer properties.
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Affiliation(s)
- Asmat Ullah
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Najeeb Ullah
- School of Biochemistry and Molecular Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Touseef Nawaz
- Faculty of Pharmacy, Gomal University, D.I. Khan, Pakistan
| | - Tariq Aziz
- School of Engineering, Westlake University, Hangzhou, Zhejiang Province, 310024, China
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13
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Wankhede D, Grover S, Hofman P. Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14246112. [PMID: 36551601 PMCID: PMC9776809 DOI: 10.3390/cancers14246112] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/04/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Background: In breast, prostate, and other epithelial tumors, circulating tumor cells (CTC) in peripheral blood may predict survival. Our study evaluated the prognostic significance of baseline and postoperative CTC in patients with early non-small cell lung cancer (NSCLC) through a meta-analytic approach. Methods: Prospective studies comparing survival outcomes between positive (CTC+) and negative CTC (CTC−) patients were systematically searched. Primary outcomes were overall (OS) and disease-free survival (DFS) with hazard ratio (HR) and 95% confidence interval (CI) as the effect measure. Pooled HR determined the prognostic role under a fixed-effect or random-effect model depending on heterogeneity. Results: Eighteen studies with 1321 patients were eligible. CTC+ patients were associated with an increased risk of death (HR 3.53, 95% CI 2.51−4.95; p < 0.00001) and relapse (HR 2.97, 95% CI 2.08−4.22; p < 0.00001). Subgroup analysis results were consistent in different subsets, including time points (baseline and postoperative) and sources (peripheral and pulmonary vein) of blood collection, detection methods (label-free, label-dependent, and RT-PCR), and follow-up duration. Conclusion: Our meta-analysis revealed that CTC is a promising predictive biomarker for stratifying survival outcomes in patients with early-stage NSCLC. However, future studies are required to validate these findings and standardize detection methods.
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Affiliation(s)
- Durgesh Wankhede
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India
- Correspondence:
| | - Sandeep Grover
- Center for Human Genetics, Universitatsklinikum Giessen und Marburg—Standort Marburg, 35055 Marburg, Germany
| | - Paul Hofman
- Laboratory of Clinical and Experimental Pathology, CHU Nice, FHU OncoAge, University Côte d’Azur, 06100 Nice, France
- Team 4, IRCAN, UMR 7284/U10181, FHU OncoAge, University Côte d’Azur, 06107 Nice, France
- Hospital-Integrated Biobank (BB-0033-00025), CHU Nice, FHU OncoAge, University Côte d’Azur, 06100 Nice, France
- European Liquid Biopsy Society, Martinistrasse 52 Building N27 Room 4.003, 20246 Hamburg, Germany
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14
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Mencel J, Slater S, Cartwright E, Starling N. The Role of ctDNA in Gastric Cancer. Cancers (Basel) 2022; 14:5105. [PMID: 36291888 PMCID: PMC9600786 DOI: 10.3390/cancers14205105] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/10/2022] [Accepted: 10/13/2022] [Indexed: 11/23/2022] Open
Abstract
Circulating tumour DNA (ctDNA) has potential applications in gastric cancer (GC) with respect to screening, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision making and therapeutic monitoring. It can provide a less invasive and convenient method to capture the tumoural genomic landscape compared to tissue-based next-generation DNA sequencing (NGS). In addition, ctDNA can potentially overcome the challenges of tumour heterogeneity seen with tissue-based NGS. Although the evidence for ctDNA in GC is evolving, its potential utility is far reaching and may shape the management of this disease in the future. This article will review the current and future applications of ctDNA in GC.
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Affiliation(s)
| | | | | | - Naureen Starling
- Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation, London SW3 6JJ, UK
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15
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Li Z, Song M, Han S, Jin C, Yang J. The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis. Front Oncol 2022; 12:963091. [PMID: 36313657 PMCID: PMC9610107 DOI: 10.3389/fonc.2022.963091] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE We conducted a meta-analysis to evaluate the relationship between circulating tumor cells (CTC) and the prognosis of patients with gastric cancer. MATERIALS AND METHODS The cohort studies reporting on the relationship between CTC and prognosis of gastric cancer were collected from Pubmed, Cochrane, Embase, CNKI, WanFang Data, and VIP databases. The two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included literature. The data were analyzed by Revman software (Review Manager version 5.4). RESULT A total of 14 retrospective cohort studies with 1053 patients were included. The results showed that the overall survival time (OS) and progression-free survival time (PFS) of CTC-positive patients were shorter compared to CTC-negative patients. Taking into consideration the critical value of CTC positive patients, country of origin, sample size, treatment mode, and study time, the subgroup analysis showed that CTC-positive was related to the shortening of OS in patients with gastric cancer. Based on the subgroup analysis of the factors such as CTC positive critical value < 2.8, sample size ≥ 75, mixed therapy, longer study duration, country, and immunofluorescence detection of CTC, it was found that OS in CTC positive group was shorter than that in CTC-negative group (all P<0.05), while the critical value of positive CTC ≥ 2.8, sample size ≥ 75, choice of treatment only for operation or non-operation, short study time and molecular detection of CTC were not associated with OS (all P>0.05). In addition, CTC-positive patients had a more advanced TNM staging, poorer tumor differentiation, and earlier distant metastasis. CONCLUSION CTC can be used as a prognostic indicator of gastric cancer. Gastric cancer patients with positive CTC may have a poorer prognosis compared to those with CTC-negative tumors. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022323155.
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Affiliation(s)
- Zuxi Li
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Meijuan Song
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Shangjun Han
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Chuanwei Jin
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Jing Yang
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
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16
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Zhi X, Kuang X, Li J. The Impact of Perioperative Events on Cancer Recurrence and Metastasis in Patients after Radical Gastrectomy: A Review. Cancers (Basel) 2022; 14:3496. [PMID: 35884557 PMCID: PMC9319233 DOI: 10.3390/cancers14143496] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/13/2022] [Accepted: 07/17/2022] [Indexed: 02/04/2023] Open
Abstract
Radical gastrectomy is a mainstay therapy for patients with locally resectable gastric cancer (GC). GC patients who are candidates for radical gastrectomy will experience at least part of the following perioperative events: surgery, anesthesia, pain, intraoperative blood loss, allogeneic blood transfusion, postoperative complications, and their related anxiety, depression and stress response. Considerable clinical studies have shown that these perioperative events can promote recurrence and decrease the long-term survival of GC patients. The mechanisms include activation of neural signaling and the inflammatory response, suppression of antimetastatic immunity, increased release of cancer cells into circulation, and delayed adjuvant therapy, which are involved in every step of the invasion-metastasis cascade. Having appreciated these perioperative events and their influence on the risk of GC recurrence, we can now use this knowledge to find strategies that might substantially prevent the deleterious recurrence-promoting effects of perioperative events, potentially increasing cancer-free survival in GC patients.
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Affiliation(s)
- Xing Zhi
- Department of General Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China;
| | - Xiaohong Kuang
- Department of Hematology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang 621000, China;
| | - Jian Li
- Department of General Surgery, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang 621000, China
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17
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Tumour invasion and dissemination. Biochem Soc Trans 2022; 50:1245-1257. [PMID: 35713387 PMCID: PMC9246329 DOI: 10.1042/bst20220452] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/16/2022] [Accepted: 05/30/2022] [Indexed: 11/17/2022]
Abstract
Activating invasion and metastasis are one of the primary hallmarks of cancer, the latter representing the leading cause of death in cancer patients. Whilst many advances in this area have been made in recent years, the process of cancer dissemination and the underlying mechanisms governing invasion are still poorly understood. Cancer cells exhibit multiple invasion strategies, including switching between modes of invasion and plasticity in response to therapies, surgical interventions and environmental stimuli. The ability of cancer cells to switch migratory modes and their inherent plasticity highlights the critical challenge preventing the successful design of cancer and anti-metastatic therapies. This mini-review presents current knowledge on the critical models of tumour invasion and dissemination. We also discuss the current issues surrounding current treatments and arising therapeutic opportunities. We propose that the establishment of novel approaches to study the key biological mechanisms underlying the metastatic cascade is critical in finding novel targets that could ultimately lead to complete inhibition of cancer cell invasion and dissemination.
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18
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Zeng Y, Huang Y, Fu J, Xu K, Liang W, Cui F, Hao Z, Li X, Xing T, He J, Liu J. Wedge resection before lobectomy for patients with T1N0M0 non-small cell lung cancer: a propensity score matching analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:502. [PMID: 35928736 PMCID: PMC9347037 DOI: 10.21037/atm-21-5246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/28/2022] [Indexed: 11/22/2022]
Abstract
Background Whether wedge resection of a tumor before lobectomy (Wed + Lob) can improve the prognosis of non-small cell lung cancer (NSCLC) has yet to be determined comprehensively. This study aimed to compare the effects of Wed + Lob with those of direct lobectomy (Lob) on survival and tumor cell dissemination in patients with T1N0M0 NSCLC. Methods A cohort of 813 patients with T1N0M0 NSCLC who underwent lobectomy at a single center in China was investigated. After propensity score matching, the overall survival (OS) and disease-free survival (DFS) of patients were estimated using Kaplan-Meier plots. Associations between surgical strategies and patient survival were computed as hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Changes in folate receptor-positive circulating tumor cells (FR+ CTCs) after lobectomy were analyzed in another cohort from our hospital. Results A total of 401 Wed + Lob cases were matched with 255 Lob cases according to their propensity scores. Although no significant differences were found in OS, multivariate analysis showed that patients with T1N0M0 NSCLC in the Wed + Lob group had significantly improved DFS (HR =0.583; P=0.012) compared to those in the Lob group. After surgery, a decrease in FR+ CTCs was observed in 21 of 23 patients (91.3%) in the Wed + Lob group and in 16 of 23 patients (69.6%) in the Lob group [mean changes: 6.10 (±7.80) FU per 3 mL vs. 1.31 (±4.39) FU per 3 mL; P=0.014]. Conclusions Wed + Lob may improve DFS and reduce tumor cell dissemination in patients with T1N0M0 NSCLC.
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Affiliation(s)
- Yuan Zeng
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Ying Huang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Junhui Fu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
- Department of Surgical Oncology, Shantou Central Hospital, Shantou, China
| | - Ke Xu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Wenhua Liang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Fei Cui
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Zhexue Hao
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Xukai Li
- Department of Thoracic Surgery, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Tuo Xing
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Jianxing He
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Jun Liu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
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19
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Carneiro A, Piairo P, Teixeira A, Ferreira D, Cotton S, Rodrigues C, Chícharo A, Abalde-Cela S, Santos LL, Lima L, Diéguez L. Discriminating Epithelial to Mesenchymal Transition Phenotypes in Circulating Tumor Cells Isolated from Advanced Gastrointestinal Cancer Patients. Cells 2022; 11:cells11030376. [PMID: 35159186 PMCID: PMC8834092 DOI: 10.3390/cells11030376] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 01/27/2023] Open
Abstract
Gastrointestinal (GI) cancers constitute a group of highest morbidity worldwide, with colorectal cancer (CRC) and gastric cancer being among the most frequently diagnosed. The majority of gastrointestinal cancer patients already present metastasis by the time of diagnosis, which is widely associated with cancer-related death. Accumulating evidence suggests that epithelial-to-mesenchymal transition (EMT) in cancer promotes circulating tumor cell (CTCs) formation, which ultimately drives metastasis development. These cells have emerged as a fundamental tool for cancer diagnosis and monitoring, as they reflect tumor heterogeneity and the clonal evolution of cancer in real-time. In particular, EMT phenotypes are commonly associated with therapy resistance. Thus, capturing these CTCs is expected to reveal important clinical information. However, currently available CTC isolation approaches are suboptimal and are often targeted to capture epithelial CTCs, leading to the loss of EMT or mesenchymal CTCs. Here, we describe size-based CTCs isolation using the RUBYchip™, a label-free microfluidic device, aiming to detect EMT biomarkers in CTCs from whole blood samples of GI cancer patients. We found that, for most cases, the mesenchymal phenotype was predominant, and in fact a considerable fraction of isolated CTCs did not express epithelial markers. The RUBYchip™ can overcome the limitations of label-dependent technologies and improve the identification of CTC subpopulations that may be related to different clinical outcomes.
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Affiliation(s)
- Adriana Carneiro
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
- IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (D.F.); (S.C.); (L.L.S.); (L.L.)
| | - Paulina Piairo
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
- Correspondence: (P.P.); (L.D.)
| | - Alexandra Teixeira
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
| | - Dylan Ferreira
- IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (D.F.); (S.C.); (L.L.S.); (L.L.)
| | - Sofia Cotton
- IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (D.F.); (S.C.); (L.L.S.); (L.L.)
| | - Carolina Rodrigues
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
| | - Alexandre Chícharo
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
| | - Sara Abalde-Cela
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
| | - Lúcio Lara Santos
- IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (D.F.); (S.C.); (L.L.S.); (L.L.)
- Department of Surgical Oncology, Portuguese Institute of Oncology (IPO Porto), 4200-072 Porto, Portugal
| | - Luís Lima
- IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (D.F.); (S.C.); (L.L.S.); (L.L.)
| | - Lorena Diéguez
- International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal; (A.C.); (A.T.); (C.R.); (A.C.); (S.A.-C.)
- Correspondence: (P.P.); (L.D.)
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20
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Lin D, Shen L, Luo M, Zhang K, Li J, Yang Q, Zhu F, Zhou D, Zheng S, Chen Y, Zhou J. Circulating tumor cells: biology and clinical significance. Signal Transduct Target Ther 2021; 6:404. [PMID: 34803167 PMCID: PMC8606574 DOI: 10.1038/s41392-021-00817-8] [Citation(s) in RCA: 466] [Impact Index Per Article: 116.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/06/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
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Affiliation(s)
- Danfeng Lin
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lesang Shen
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Meng Luo
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kun Zhang
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinfan Li
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi Yang
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fangfang Zhu
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Zhou
- Department of Surgery, Traditional Chinese Medical Hospital of Zhuji, Shaoxing, China
| | - Shu Zheng
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiding Chen
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Jiaojiao Zhou
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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21
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Ding J, Zhang Y, Cai X, Diao L, Yang C, Yang J. Crosstalk Between Trophoblast and Macrophage at the Maternal-Fetal Interface: Current Status and Future Perspectives. Front Immunol 2021; 12:758281. [PMID: 34745133 PMCID: PMC8566971 DOI: 10.3389/fimmu.2021.758281] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 10/06/2021] [Indexed: 12/31/2022] Open
Abstract
The immune tolerance microenvironment is crucial for the establishment and maintenance of pregnancy at the maternal-fetal interface. The maternal-fetal interface is a complex system containing various cells, including lymphocytes, decidual stromal cells, and trophoblasts. Macrophages are the second-largest leukocytes at the maternal-fetal interface, which has been demonstrated to play essential roles in remodeling spiral arteries, maintaining maternal-fetal immune tolerance, and regulating trophoblast's biological behaviors. Many researchers, including us, have conducted a series of studies on the crosstalk between macrophages and trophoblasts at the maternal-fetal interface: on the one hand, macrophages can affect the invasion and migration of trophoblasts; on the other hand, trophoblasts can regulate macrophage polarization and influence the state of the maternal-fetal immune microenvironment. In this review, we systemically introduce the functions of macrophages and trophoblasts and the cell-cell interaction between them for the establishment and maintenance of pregnancy. Advances in this area will further accelerate the basic research and clinical translation of reproductive medicine.
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Affiliation(s)
- Jinli Ding
- Reproductive Medical Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China
| | - Yan Zhang
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaopeng Cai
- Department of Gastrointestinal Surgery, The Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Lianghui Diao
- Shenzhen Key Laboratory of Reproductive Immunology for Periimplantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Urology Hospital, Shenzhen, China
| | - Chaogang Yang
- Department of Gastrointestinal Surgery, The Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jing Yang
- Reproductive Medical Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China
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22
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Li LS, Guo XY, Sun K. Recent advances in blood-based and artificial intelligence-enhanced approaches for gastrointestinal cancer diagnosis. World J Gastroenterol 2021; 27:5666-5681. [PMID: 34629793 PMCID: PMC8473600 DOI: 10.3748/wjg.v27.i34.5666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/14/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancers are among the most common cancer types and leading causes of cancer-related deaths worldwide. There is a tremendous clinical need for effective early diagnosis for better healthcare of GI cancer patients. In this article, we provide a short overview of the recent advances in GI cancer diagnosis. In the first part, we discuss the applications of blood-based biomarkers, such as plasma circulating cell-free DNA, circulating tumor cells, extracellular vesicles, and circulating cell-free RNA, for cancer liquid biopsies. In the second part, we review the current trends of artificial intelligence (AI) for pathology image and tissue biopsy analysis for GI cancer, as well as deep learning-based approaches for purity assessment of tissue biopsies. We further provide our opinions on the future directions in blood-based and AI-enhanced approaches for GI cancer diagnosis, and we think that these fields will have more intensive integrations with clinical needs in the near future.
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Affiliation(s)
- Li-Shi Li
- School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen 518055, Guangdong Province, China
- Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, Guangdong Province, China
| | - Xiang-Yu Guo
- Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, Guangdong Province, China
| | - Kun Sun
- Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, Guangdong Province, China
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
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23
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Jiang Q, Sun J, Chen H, Ding C, Tang Z, Ruan Y, Liu F, Sun Y. Establishment of an Immune Cell Infiltration Score to Help Predict the Prognosis and Chemotherapy Responsiveness of Gastric Cancer Patients. Front Oncol 2021; 11:650673. [PMID: 34307129 PMCID: PMC8299334 DOI: 10.3389/fonc.2021.650673] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 06/22/2021] [Indexed: 12/24/2022] Open
Abstract
The immune microenvironment plays a critical role in tumor biology. The molecular profiles of immune components and related genes are of tremendous value for the study of primary resistance to immune checkpoint blockers (ICBs) for gastric cancer (GC) and serve as prognostic biomarkers to predict GC survival. Recent studies have revealed that tumor immune cell infiltration (ICI) is an indicator of the survival and responsiveness to chemotherapy in GC patients. Here, we describe the immune cell landscape based on the ESTIMATE and CIBERSORT algorithms to help separate GC into 3 ICI clusters using the unsupervised clustering method. Further in-depth analyses, such as differential expression gene (DEG) analysis and principal component analysis (PCA), help to establish an ICI scoring system. A low ICI score is characterized by an increased tumor mutation burden (TMB). The combination of the ICI score and TMB score better predicts the survival of GC patients. Analyses based on public and our own database revealed that the ICI scoring system could also help predict the survival and chemotherapy responsiveness of GC patients. The present study demonstrated that the ICI score may be an effective prognostic biomarker and predictive indicator for chemotherapy and immunotherapy.
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Affiliation(s)
- Quan Jiang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Human Phenome Institute, Fudan University, Shanghai, China
| | - Jie Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chen Ding
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaoqing Tang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuanyuan Ruan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Fenglin Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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24
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Lengyel CG, Hussain S, Trapani D, El Bairi K, Altuna SC, Seeber A, Odhiambo A, Habeeb BS, Seid F. The Emerging Role of Liquid Biopsy in Gastric Cancer. J Clin Med 2021; 10:2108. [PMID: 34068319 PMCID: PMC8153353 DOI: 10.3390/jcm10102108] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/07/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages. In the setting of localized disease, cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) qualitative and quantitative detection have the potential to inform on the risk of cancer recurrence and metastatic dissemination. In addition, gastric cancer-released exosomes may play an essential part in metastasis formation. In the metastatic setting, the levels of cfDNA show a positive correlation with tumor burden. There is evidence that circulating tumor microemboli (CTM) in the blood of metastatic patients is an independent prognostic factor for shorter overall survival. Gastric cancer-derived exosomal microRNAs or clonal mutations and copy number variations detectable in ctDNA may contribute resistance to chemotherapy or targeted therapies, respectively. There is conflicting and limited data on CTC-based PD-L1 verification and cfDNA-based Epstein-Barr virus detection to predict or monitor immunotherapy responses. (4) Conclusions: Although preliminary studies analyzing LBs in patients with advanced gastric cancer appear promising, more research is required to obtain better insights into the molecular mechanisms underlying resistance to systemic therapies. Moreover, validation and standardization of LB methods are crucial before introducing them in clinical practice. The feasibility of repeatable, minimally invasive sampling opens up the possibility of selecting or dynamically changing therapies based on prognostic risk or predictive biomarkers, such as resistance markers. Research is warranted to exploit a possible transforming area of cancer care.
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Affiliation(s)
| | - Sadaqat Hussain
- North West Cancer Center, Altnagelvin Hospital, Londonderry BT47 6SB, UK;
| | - Dario Trapani
- European Institute of Oncology, IRCCS, 20141 Milan, Italy;
| | | | | | - Andreas Seeber
- Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - Andrew Odhiambo
- Unit of Medical Oncology, Department of Clinical Medicine, University of Nairobi, Nairobi 30197, Kenya;
| | - Baker Shalal Habeeb
- Department of Medical Oncology, Shaqlawa Teaching Hospital, Shaqlawa, Erbil 44005, Iraq;
| | - Fahmi Seid
- School of Medicine and Health Sciences, Hawassa University, Hawassa 1560, Ethiopia;
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25
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Neuroimmune Regulation of Surgery-Associated Metastases. Cells 2021; 10:cells10020454. [PMID: 33672617 PMCID: PMC7924204 DOI: 10.3390/cells10020454] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/12/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Surgery remains an essential therapeutic approach for most solid malignancies. Although for more than a century accumulating clinical and experimental data have indicated that surgical procedures themselves may promote the appearance and progression of recurrent and metastatic lesions, only in recent years has renewed interest been taken in the mechanism by which metastasizing of cancer occurs following operative procedures. It is well proven now that surgery constitutes a risk factor for the promotion of pre-existing, possibly dormant micrometastases and the acceleration of new metastases through several mechanisms, including the release of neuroendocrine and stress hormones and wound healing pathway-associated immunosuppression, neovascularization, and tissue remodeling. These postoperative consequences synergistically facilitate the establishment of new metastases and the development of pre-existing micrometastases. While only in recent years the role of the peripheral nervous system has been recognized as another contributor to cancer development and metastasis, little is known about the contribution of tumor-associated neuronal and neuroglial elements in the metastatic disease related to surgical trauma and wound healing. Specifically, although numerous clinical and experimental data suggest that biopsy- and surgery-induced wound healing can promote survival and metastatic spread of residual and dormant malignant cells, the involvement of the tumor-associated neuroglial cells in the formation of metastases following tissue injury has not been well understood. Understanding the clinical significance and underlying mechanisms of neuroimmune regulation of surgery-associated metastasis will not only advance the field of neuro–immuno–oncology and contribute to basic science and translational oncology research but will also produce a strong foundation for developing novel mechanism-based therapeutic approaches that may protect patients against the oncologically adverse effects of primary tumor biopsy and excision.
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26
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Leja M, Linē A. Early detection of gastric cancer beyond endoscopy - new methods. Best Pract Res Clin Gastroenterol 2021; 50-51:101731. [PMID: 33975677 DOI: 10.1016/j.bpg.2021.101731] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/08/2021] [Indexed: 01/31/2023]
Abstract
Early detection of gastric cancer is remaining a challenge. This review summarizes current knowledge on non-invasive methods that could be used for the purpose. The role of traditional cancer markers such as CEA, CA 72-4, CA 19-9, CA 15-3, and CA 12-5 lies mainly in therapy monitoring than early detection. Most extensive studied biomarkers (pepsinogens, ABC method) are aiming at the detection of precancerous lesions with modest sensitivity for cancer. Tests based on the detection of cancer-specific methylation patterns (PanSeer), circulating proteins and mutations in circulating tumour DNA (CancerSEEK), as well as miRNA panels have demonstrated promising results bringing those closer to practice. More extensive research is required before tests based on the detection of circulating tumour cells, extracellular vesicles and cell-free RNA could reach the practice. Detection of volatile organic compounds in the human breath is a promising development; sensor technologies for this purpose could be very attractive in screening settings.
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Affiliation(s)
- Mārcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, 1 Gailezera iela iela, LV1079, Riga, Latvia.
| | - Aija Linē
- Latvian Biomedical Research and Study Centre, Latvia.
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27
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Wu C, Zhang J, Li H, Xu W, Zhang X. The potential of liquid biopsies in gastrointestinal cancer. Clin Biochem 2020; 84:1-12. [PMID: 32540214 DOI: 10.1016/j.clinbiochem.2020.06.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/09/2020] [Accepted: 06/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liquid biopsy is a novel approach for cancer diagnosis, the value of which in human gastrointestinal (GI) cancer has been confirmed by the previous studies. This article summarized the recent advances in liquid biopsy with a focus on novel technologies and the use of it in the screening, monitoring, and treatment of human GI cancer. CONTENT The concept of liquid biopsy was first used to define the detection of circulating tumor cells (CTCs) in cancer patients, and has been expanded to other biomarkers in blood and body fluids, such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs) and circulating tumor RNA. If analyzed with proper and advanced techniques like next generation sequencing (NGS) or proteomics, liquid biopsies can open an enormous array of potential biomarkers. The amount changes of target biomarkers and the mutation of genetic materials provide quantitative and qualitative information, which can be utilized clinically for cancer diagnosis and disease monitoring. SUMMARY As a highly efficient, minimally invasive, and cost-effective approach to diagnose and evaluate prognosis of GI cancer, liquid biopsy has lots of advantages over traditional biopsy and is promising in future clinical utility. If the challenges are overcome in the near future, liquid biopsy will become a widely available and dependable option.
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Affiliation(s)
- Chenxi Wu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Jiayin Zhang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Haibo Li
- Department of Clinical Laboratory, Nantong Maternal and Child Health Care Hospital, Nantong, Jiangsu 226000, China
| | - Wenrong Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Xu Zhang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
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28
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Yang C, Chen F, Wang S, Xiong B. Circulating Tumor Cells in Gastrointestinal Cancers: Current Status and Future Perspectives. Front Oncol 2019; 9:1427. [PMID: 31921680 PMCID: PMC6923205 DOI: 10.3389/fonc.2019.01427] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 11/29/2019] [Indexed: 12/24/2022] Open
Abstract
Circulating tumor cells (CTCs), which are now defined as the "break away" cancer cells that derive from primary- or metastatic-tumor sites and present in the bloodstream, are considered to be the precursors of metastases. Considering the key role of CTCs in cancer progression, researchers are committed to analyze them in the past decades and many technologies have been proposed for achieving CTCs isolation and characterization with highly sensitivity and specificity until now. On this basis, clinicians gradually realize the clinical values of CTCs' detection through various clinical studies. As a "liquid biopsy," CTCs' detection and measurement can supply important information for predicting patient's survival, monitoring of response/resistance, assessment of minimal residual disease, evaluating distant metastasis, and sometimes, customizing therapy choices. Nowadays, eliminating CTCs of the blood circulation has been regarded as a promising method to prevent tumor metastasis. However, research on CTCs still faces many challenges. Herein, we present an overview to discuss the current concept of CTCs, summarize the available techniques for CTCs detection, and provide an update on the clinical significance of CTCs in gastrointestinal malignancies, especially focus on gastric and colorectal cancer.
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Affiliation(s)
- Chaogang Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
| | - Fangfang Chen
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China.,Department of Breast and Thyroid Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shuyi Wang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
| | - Bin Xiong
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
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29
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Chen Z, Zhang P, Xu Y, Yan J, Liu Z, Lau WB, Lau B, Li Y, Zhao X, Wei Y, Zhou S. Surgical stress and cancer progression: the twisted tango. Mol Cancer 2019; 18:132. [PMID: 31477121 PMCID: PMC6717988 DOI: 10.1186/s12943-019-1058-3] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 08/14/2019] [Indexed: 12/20/2022] Open
Abstract
Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.
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Affiliation(s)
- Zhiwei Chen
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Peidong Zhang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Ya Xu
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China.,Deyang People's Hospital, Deyang, Sichuan, People's Republic of China
| | - Jiahui Yan
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Zixuan Liu
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Wayne Bond Lau
- Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, USA
| | - Bonnie Lau
- Department of Surgery, Emergency Medicine, Kaiser Santa Clara Medical Center, Affiliate of Stanford University, Stanford, USA
| | - Ying Li
- Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, People's Republic of China
| | - Xia Zhao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Yuquan Wei
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China
| | - Shengtao Zhou
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, People's Republic of China.
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