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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% confidence interval: 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% confidence interval: 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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Janjua D, Chaudhary A, Joshi U, Tripathi T, Bharti AC. Circulating tumor cells in solid malignancies: From advanced isolation technologies to biological understanding and clinical relevance in early diagnosis and prognosis. Biochim Biophys Acta Rev Cancer 2025; 1880:189236. [PMID: 39662757 DOI: 10.1016/j.bbcan.2024.189236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/03/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Circulating tumor cells (CTCs) are shed from primary tumors and travel through the body via circulation, eventually settling to form micrometastases under favorable conditions. Numerous studies have identified CTCs as a negative prognostic indicator for survival across various cancer types. CTCs mirror the current heterogeneity and genetic and biological state of tumors, making their study invaluable for understanding tumor progression, cell senescence, and cancer dormancy. However, their isolation and characterization still poses a major challenge that limits their clinical translation. A wide array of methods, each with different levels of specificity, utility, cost, and sensitivity, have been developed to isolate and characterize CTCs. Moreover, innovative techniques are emerging to address the limitations of existing methods. In this review, we provide insights into CTC biology addressing spectra of markers employed for molecular analysis and functional characterization. It also emphasizes current label-dependent and label-independent isolation procedures, addressing their strengths and limitations. SIGNIFICANCE: A comprehensive overview of CTC biology, their molecular and functional characterization, along with their current clinical utility will help in understanding the present-day extent to which the clinical potential of CTCs is getting tapped in personalized medicine.
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Affiliation(s)
- Divya Janjua
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India
| | - Apoorva Chaudhary
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India
| | - Udit Joshi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India
| | - Tanya Tripathi
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India
| | - Alok Chandra Bharti
- Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India.
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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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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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Zhang J, Hong Y, Wang L, Hu W, Tian G, Wu D, Wang Y, Dai L, Zhang Z, Yang Y, Fang J. Aneuploid subtypes of circulating tumor cells and circulating tumor-derived endothelial cells predict the overall survival of advanced lung cancer. Front Oncol 2023; 13:829054. [PMID: 37213309 PMCID: PMC10196356 DOI: 10.3389/fonc.2023.829054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 04/18/2023] [Indexed: 05/23/2023] Open
Abstract
Objective This study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers. Methods A total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified. Results Based on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P<0.0001) in the four groups including triploid small cell size CTCs and multiploid small cell size CTECs, and multiploid small cell size CTCs and monoploid small cell size CTECs. Furthermore, combined detection of the specific subtypes, including triploid small CTC and monoploid small CTEC, triploid small CTC and triploid small CTEC, and multiploid small CTC and monoploid small CTEC, were associated with poor prognosis in advanced lung cancer. Conclusions Aneuploid small CTCs are associated with the outcome of patients with advanced lung cancer. In particular, the combined detection of triploid small CTCs and monoploid small CTECs, triploid small CTCs and triploid small CTECs, and multiploid small CTCs and monoploid small CTECs has clinical significance for predicting prognosis in patients with advanced lung cancer.
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Affiliation(s)
- Jie Zhang
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yang Hong
- Department of Anesthesiology, China-Japan Friendship Hospital, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
- Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Liang Wang
- Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Weiheng Hu
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Guangming Tian
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Di Wu
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yang Wang
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Ling Dai
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Ziran Zhang
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yue Yang
- Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Jian Fang
- Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
- *Correspondence: Jian Fang,
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7
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Zhang Z, Wu H, Chong W, Shang L, Jing C, Li L. Liquid biopsy in gastric cancer: predictive and prognostic biomarkers. Cell Death Dis 2022; 13:903. [PMID: 36302755 PMCID: PMC9613678 DOI: 10.1038/s41419-022-05350-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 10/12/2022] [Accepted: 10/14/2022] [Indexed: 11/11/2022]
Abstract
Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.
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Affiliation(s)
- Zihao Zhang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
| | - Hao Wu
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250021, China
- Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Chong
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250021, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, 250021, China.
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250021, China.
| | - Changqing Jing
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, 250021, China.
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250021, China.
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, 250021, China.
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250021, China.
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Tao J, Zhu L, Yakoub M, Reißfelder C, Loges S, Schölch S. Cell-Cell Interactions Drive Metastasis of Circulating Tumor Microemboli. Cancer Res 2022; 82:2661-2671. [PMID: 35856896 DOI: 10.1158/0008-5472.can-22-0906] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/27/2022] [Accepted: 06/13/2022] [Indexed: 11/16/2022]
Abstract
Circulating tumor cells are the cellular mediators of distant metastasis in solid malignancies. Their metastatic potential can be augmented by clustering with other tumor cells or nonmalignant cells, forming circulating tumor microemboli (CTM). Cell-cell interactions are key regulators within CTM that convey enhanced metastatic properties, including improved cell survival, immune evasion, and effective extravasation into distant organs. However, the cellular and molecular mechanism of CTM formation, as well as the biology of interactions between tumor cells and immune cells, platelets, and stromal cells in the circulation, remains to be determined. Here, we review the current literature on cell-cell interactions in homotypic and heterotypic CTM and provide perspectives on therapeutic strategies to attenuate CTM-mediated metastasis by targeting cell-cell interactions.
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Affiliation(s)
- Jianxin Tao
- JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany.,DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lei Zhu
- JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany.,DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Mina Yakoub
- JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany.,DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reißfelder
- DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Sonja Loges
- DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Personalized Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Sebastian Schölch
- JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany.,DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.,Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Wu M, Huang Y, Zhou Y, Zhao H, Lan Y, Yu Z, Jia C, Cong H, Zhao J. The Discovery of Novel Circulating Cancer-Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection. SMALL METHODS 2022; 6:e2200226. [PMID: 35595707 DOI: 10.1002/smtd.202200226] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/19/2022] [Indexed: 06/15/2023]
Abstract
Circulating tumor cells (CTCs) enumeration has been widely used as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. Microfluidic technologies for CTCs enrichment and detection have been developed and commercialized as automation platforms. Currently, in addition to CTCs, some new types of circulating cancer-related cells (e.g., CCSCs, CTECs, CAMLs, and heterotypic CTC clusters) in circulation are also reported to be correlated to cancer diagnosis, metastasis, or prognosis. And they widely differ from the conventional CTCs in positive markers, cellular morphology, or size, which presents a new technological challenge to microfluidic devices that use affinity-based capture methods or size-based filtration methods for CTCs detection. This review focuses on the biological and physical properties as well as clinical significance of the novel circulating cancer-related cells, and discusses the challenges of their discovery to microfluidic chip for enrichment. Finally, the current challenges of CTCs detection in clinical application and future opportunities are also discussed.
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Affiliation(s)
- Man Wu
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuhang Huang
- Shanghai Normal University, Shanghai, 200030, China
| | - Yang Zhou
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Hui Zhao
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuwei Lan
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhibin Yu
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Chunping Jia
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Hui Cong
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Jianlong Zhao
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
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