Skip to main content

Advertisement

SpringerLink
Log in

Circulating tumor cells in gastric cancer: developments and clinical applications

  • Review
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    PubMed  Google Scholar 

  2. Marrelli D, De Stefano A, de Manzoni G, et al. Prediction of recurrence after radical surgery for gastric cancer: a scoring system obtained from a prospective multicenter study. Ann Surg. 2005;241:247–55.

    PubMed  PubMed Central  Google Scholar 

  3. Thanh Huong P, Gurshaney S, Thanh Binh N, et al. Emerging role of circulating tumor cells in gastric cancer. Cancers (Basel). 2020;12:695.

  4. Li Y, Yang Y, Lu M, Shen L. Predictive value of serum CEA, CA19–9 and CA72.4 in early diagnosis of recurrence after radical resection of gastric cancer. Hepatogastroenterology. 2011;58:2166–70.

    CAS  PubMed  Google Scholar 

  5. Ashworth T. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J. 1869;14:146.

    Google Scholar 

  6. Aceto N, Bardia A, Miyamoto DT, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158:1110–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.

    CAS  PubMed  Google Scholar 

  8. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14:6302–9.

    PubMed  Google Scholar 

  9. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3213–21.

    PubMed  Google Scholar 

  10. Cui L, Lou Y, Zhang X, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011;44:1050–7.

    CAS  PubMed  Google Scholar 

  11. Kutun S, Celik A, Cem Kockar M, et al. Expression of CK-19 and CEA mRNA in peripheral blood of gastric cancer patients. Exp Oncol. 2010;32:263–8.

    CAS  PubMed  Google Scholar 

  12. Arigami T, Uenosono Y, Hirata M, et al. B7–H3 expression in gastric cancer: a novel molecular blood marker for detecting circulating tumor cells. Cancer Sci. 2011;102:1019–24.

    CAS  PubMed  Google Scholar 

  13. Uen YH, Lin SR, Wu CH, et al. Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor cells in patients with gastric carcinoma. Clin Chim Acta. 2006;367:55–61.

    CAS  PubMed  Google Scholar 

  14. Zhou H, Guo JM, Lou YR, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med (Berl). 2010;88:709–17.

    CAS  PubMed  Google Scholar 

  15. Arigami T, Uenosono Y, Ishigami S, et al. Clinical significance of stanniocalcin 2 expression as a predictor of tumor progression in gastric cancer. Oncol Rep. 2013;30:2838–44.

    CAS  PubMed  Google Scholar 

  16. Lambrechts AC, Bosma AJ, Klaver SG, et al. Comparison of immunocytochemistry, reverse transcriptase polymerase chain reaction, and nucleic acid sequence-based amplification for the detection of circulating breast cancer cells. Breast Cancer Res Treat. 1999;56:219–31.

    CAS  PubMed  Google Scholar 

  17. Pantel K, Cote RJ, Fodstad O. Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst. 1999;91:1113–24.

    CAS  PubMed  Google Scholar 

  18. Arigami T, Uenosono Y, Yanagita S, et al. Clinical significance of circulating tumor cells in blood from patients with gastric cancer. Ann Gastroenterol Surg. 2017;1:60–8.

    PubMed  PubMed Central  Google Scholar 

  19. Zhang ZY, Ge HY. Micrometastasis in gastric cancer. Cancer Lett. 2013;336:34–45.

    CAS  PubMed  Google Scholar 

  20. Wenqi D, Li W, Shanshan C, et al. EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol. 2009;135:1277–85.

    PubMed  Google Scholar 

  21. Ishiguro Y, Sakihama H, Yoshida T, et al. Prognostic significance of circulating tumor cells with mesenchymal phenotypes in patients with gastric cancer: a prospective study. Ann Surg Oncol. 2021;28:1178–86.

    PubMed  Google Scholar 

  22. Lei KF. A review on microdevices for isolating circulating tumor cells. Micromachines (Basel). 2020;11:531.

  23. Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ. Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv. 2013;31:1063–84.

    CAS  PubMed  Google Scholar 

  24. Neves M, Azevedo R, Lima L, et al. Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells: a novel biomarker and an analytical tool for precision oncology applications. New Biotechnol. 2019;49:77–87.

    CAS  Google Scholar 

  25. Qin L, Zhou W, Zhang S, et al. Highly efficient isolation of circulating tumor cells using a simple wedge-shaped microfluidic device. IEEE Trans Biomed Eng. 2019;66:1536–41.

    PubMed  Google Scholar 

  26. Pecot CV, Bischoff FZ, Mayer JA, et al. A novel platform for detection of CK+ and CK- CTCs. Cancer Discov. 2011;1:580–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Nagrath S, Sequist LV, Maheswaran S, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Stott SL, Hsu CH, Tsukrov DI, et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A. 2010;107:18392–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Ozkumur E, Shah AM, Ciciliano JC, et al. Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med. 2013;5:179ra47.

    Google Scholar 

  30. Kamande JW, Hupert ML, Witek MA, et al. Modular microsystem for the isolation, enumeration, and phenotyping of circulating tumor cells in patients with pancreatic cancer. Anal Chem. 2013;85:9092–100.

    CAS  PubMed  Google Scholar 

  31. Huang X, Gao P, Sun J, et al. Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: a meta-analysis. Int J Cancer. 2015;136:21–33.

    CAS  PubMed  Google Scholar 

  32. Uenosono Y, Arigami T, Kozono T, et al. Clinical significance of circulating tumor cells in peripheral blood from patients with gastric cancer. Cancer. 2013;119:3984–91.

    PubMed  Google Scholar 

  33. Illert B, Fein M, Otto C, et al. Disseminated tumor cells in the blood of patients with gastric cancer are an independent predictive marker of poor prognosis. Scand J Gastroenterol. 2009;40:843–9.

    Google Scholar 

  34. Zhang Q, Shan F, Li Z, et al. A prospective study on the changes and clinical significance of pre-operative and post-operative circulating tumor cells in resectable gastric cancer. J Transl Med. 2018;16:171.

  35. Wang FH, Zhang XT, Li YF, et al. The Chinese society of clinical oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2021. Cancer Commun (Lond). 2021;41:747–95.

    PubMed  Google Scholar 

  36. Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.

    CAS  PubMed  Google Scholar 

  37. Miyazono F, Natsugoe S, Takao S, et al. Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery. Ann Surg. 2001;233:189-94.

  38. Ikeguchi M, Kaibara N. Detection of circulating cancer cells after a gastrectomy for gastric cancer. Surg Today. 2005;35:436–41.

    CAS  PubMed  Google Scholar 

  39. Pituch-Noworolska A, Kolodziejczyk P, Kulig J, et al. Circulating tumour cells and survival of patients with gastric cancer. Anticancer Res. 2007;27:635–40.

    PubMed  Google Scholar 

  40. Hoffmann AC, Wang S, Zheng G, et al. Circulating tumor cells (CTCs) detected by RT-PCR and its prognostic role in gastric cancer: a meta-analysis of published literature. PLoS ONE. 2014;9:e99259.

  41. Vafaei S, Roudi R, Madjd Z, et al. Potential theranostics of circulating tumor cells and tumor-derived exosomes application in colorectal cancer. Cancer Cell Int. 2020;20:288.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Meulendijks D, de Groot JW, Los M, et al. Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: a multicenter phase 2 study. Cancer. 2016;122:1434–43.

    CAS  PubMed  Google Scholar 

  43. Sclafani F, Smyth E, Cunningham D, et al. A pilot study assessing the incidence and clinical significance of circulating tumor cells in esophagogastric cancers. Clin Colorectal Cancer. 2014;13:94–9.

    PubMed  Google Scholar 

  44. Matsusaka S, Chìn K, Ogura M, et al. Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer. Cancer Sci. 2010;101:1067–71.

    CAS  PubMed  Google Scholar 

  45. Li Y, Gong J, Zhang Q, et al. Dynamic monitoring of circulating tumour cells to evaluate therapeutic efficacy in advanced gastric cancer. Br J Cancer. 2016;114:138–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Inoue M, Otsuka K, Shibata H. Circulating tumor cell count as a biomarker of a specific gastric cancer subgroup characterized by bone metastasis and/or disseminated intravascular coagulation—an early indicator of chemotherapeutic response. Oncol Lett. 2016;11:1294–8.

    PubMed  Google Scholar 

  47. Shimazu K, Fukuda K, Yoshida T, et al. High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis. World J Gastroenterol. 2016;22:6083–8.

    PubMed  PubMed Central  Google Scholar 

  48. Pernot S, Badoual C, Terme M, et al. Dynamic evaluation of circulating tumour cells in patients with advanced gastric and oesogastric junction adenocarcinoma: prognostic value and early assessment of therapeutic effects. Eur J Cancer. 2017;79:15–22.

    PubMed  Google Scholar 

  49. Zhang ZY, Dai ZL, Yin XW, et al. Meta-analysis shows that circulating tumor cells including circulating microRNAs are useful to predict the survival of patients with gastric cancer. BMC Cancer. 2014;14:773.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Okabe H, Tsunoda S, Hosogi H, et al. Circulating tumor cells as an independent predictor of survival in advanced gastric cancer. Ann Surg Oncol. 2015;22:3954–61.

    CAS  PubMed  Google Scholar 

  51. Lee SJ, Lee J, Kim ST, et al. Circulating tumor cells are predictive of poor response to chemotherapy in metastatic gastric cancer. Int J Biol Markers. 2015;30:382–6.

    Google Scholar 

  52. Li Y, Zhang X, Gong J, et al. Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer. Chin J Cancer Res. 2016;28:579–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu Y, Ling Y, Qi Q, et al. Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy. Mol Clin Oncol. 2017;6:235–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kang HM, Kim GH, Jeon HK, et al. Circulating tumor cells detected by lab-on-a-disc: role in early diagnosis of gastric cancer. PLoS ONE. 2017;12:e0180251.

    PubMed  PubMed Central  Google Scholar 

  55. Cheng B, Tong G, Wu X, et al. Enumeration and characterization of circulating tumor cells and its application in advanced gastric cancer</p>. Onco Targets Ther. 2019;12:7887–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Qian C, Cai R, Zhang W, et al. Neutrophil-lymphocyte ratio and circulating tumor cells counts predict prognosis in gastrointestinal cancer patients. Front Oncol. 2021;11:710704.

    PubMed  PubMed Central  Google Scholar 

  57. Chen YL, Huang WC, Lin FM, et al. Novel circulating tumor cell-based blood test for the assessment of PD-L1 protein expression in treatment-naive, newly diagnosed patients with non-small cell lung cancer. Cancer Immunol Immunother. 2019;68:1087–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Guibert N, Delaunay M, Lusque A, et al. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Lung Cancer. 2018;120:108–12.

    PubMed  Google Scholar 

  59. Sinoquet L, Jacot W, Gauthier L, et al. Programmed cell death ligand 1-expressing circulating tumor cells: a new prognostic biomarker in non-small cell lung cancer. Clin Chem. 2021;67:1503–12.

    PubMed  Google Scholar 

  60. Winograd P, Hou S, Court CM, et al. Hepatocellular carcinoma-circulating tumor cells expressing PD-L1 are prognostic and potentially associated with response to checkpoint inhibitors. Hepatol Commun. 2020;4:1527–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4:e180013.

    PubMed  PubMed Central  Google Scholar 

  62. Yue C, Jiang Y, Li P, et al. Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy. Oncoimmunology. 2018;7:e1438111.

    PubMed  PubMed Central  Google Scholar 

  63. Janning M, Kobus F, Babayan A, et al. Determination of PD-L1 expression in circulating tumor cells of NSCLC patients and correlation with response to PD-1/PD-L1 inhibitors. Cancers (Basel). 2019;11:835.

  64. Raimondi L, Raimondi FM, Di Benedetto L, et al. PD-L1 expression on circulating tumour cells may be predictive of response to regorafenib in patients diagnosed with chemorefractory metastatic colorectal cancer. Int J Mol Sci. 2020;21:6907.

  65. Chikamatsu K, Tada H, Takahashi H, et al. Expression of immune-regulatory molecules in circulating tumor cells derived from patients with head and neck squamous cell carcinoma. Oral Oncol. 2019;89:34–9.

    CAS  PubMed  Google Scholar 

  66. Tomita Y, Oronsky B, Abrouk N, et al. In small cell lung cancer patients treated with RRx-001, a downregulator of CD47, decreased expression of PD-L1 on circulating tumor cells significantly correlates with clinical benefit. Transl Lung Cancer Res. 2021;10:274–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Manjunath Y, Upparahalli SV, Avella DM, et al. PD-L1 expression with epithelial mesenchymal transition of circulating tumor cells is associated with poor survival in curatively resected non-small cell lung cancer. Cancers (Basel). 2019;11:806.

  68. Liu M, Wang R, Sun X, et al. Prognostic significance of PD-L1 expression on cell-surface vimentin-positive circulating tumor cells in gastric cancer patients. Mol Oncol. 2020;14:865–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Kotsakis A, Kallergi G, Aggouraki D, et al. CD8(+) PD-1(+) T-cells and PD-L1(+) circulating tumor cells in chemotherapy-naive non-small cell lung cancer: towards their clinical relevance? Ther Adv Med Oncol. 2019;11:1758835919853193.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Godoy-Ortiz A, Alba-Bernal A, Pascual J, et al. Unveiling the potential of liquid biopsy in HER2-positive breast cancer management. Cancers (Basel). 2022;14:587.

  71. Loibl S, Poortmans P, Morrow M, et al. Breast cancer. The Lancet. 2021;397:1750–69.

    CAS  Google Scholar 

  72. Warneke VS, Behrens HM, Boger C, et al. Her2/neu testing in gastric cancer: evaluating the risk of sampling errors. Ann Oncol. 2013;24:725–33.

    CAS  PubMed  Google Scholar 

  73. Muller V, Banys-Paluchowski M, Friedl TWP, et al. Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program. ESMO Open. 2021;6:100299.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Flores LM, Kindelberger DW, Ligon AH, et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer. 2010;102:1495–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Iwatsuki M, Toyoshima K, Watanabe M, et al. Frequency of HER2 expression of circulating tumour cells in patients with metastatic or recurrent gastrointestinal cancer. Br J Cancer. 2013;109:2829–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Huai J, Cao M, Jiang Y, et al. Evaluation of liquid biopsy in patients with HER2-positive breast cancer. Biomed Res Int. 2021;2021:6388492.

    PubMed  PubMed Central  Google Scholar 

  77. Mishima Y, Matsusaka S, Chin K, et al. Detection of HER2 amplification in circulating tumor cells of HER2-negative gastric cancer patients. Target Oncol. 2017;12:341–51.

    PubMed  Google Scholar 

  78. Wang C, Mu Z, Ye Z, et al. Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors. Breast Cancer Res Treat. 2020;181:679–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Barok M, Balazs M, Nagy P, et al. Trastuzumab decreases the number of circulating and disseminated tumor cells despite trastuzumab resistance of the primary tumor. Cancer Lett. 2008;260:198–208.

    CAS  PubMed  Google Scholar 

  80. Price-Schiavi SA, Jepson S, Li P, et al. Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance. Int J Cancer. 2002;99:783–91.

    CAS  PubMed  Google Scholar 

  81. Palyi-Krekk Z, Barok M, Isola J, et al. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer. Eur J Cancer. 2007;43:2423–33.

    CAS  PubMed  Google Scholar 

  82. Jordan NV, Bardia A, Wittner BS, et al. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016;537:102–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Medford AJ, Dubash TD, Juric D, et al. Blood-based monitoring identifies acquired and targetable driver HER2 mutations in endocrine-resistant metastatic breast cancer. npj Precis Oncol. 2019;3:18.

  84. Li Y, Zhang X, Liu D, et al. Evolutionary expression of HER2 conferred by chromosome aneuploidy on circulating gastric cancer cells contributes to developing targeted and chemotherapeutic resistance. Clin Cancer Res. 2018;24:5261–71.

    CAS  PubMed  Google Scholar 

  85. Shoda K, Ichikawa D, Fujita Y, et al. Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer. Gastric Cancer. 2017;20:126–35.

    CAS  PubMed  Google Scholar 

  86. Liu Y, Yang M, Jiang T, et al. Quantitative analysis of HER2 amplification by droplet digital PCR in the follow-up of gastric cancer patients being treated with trastuzumab after surgery. Gastroenterol Res Pract. 2019;2019:1750329.

    PubMed  PubMed Central  Google Scholar 

  87. Uguen A. About HER2 monitoring using liquid biopsies in patients with gastric cancer. Gastric Cancer. 2017;20:1011–2.

    CAS  PubMed  Google Scholar 

  88. Fan L, Chong X, Zhao M, et al. Ultrasensitive gastric cancer circulating tumor cellular CLDN18.2 RNA detection based on a molecular beacon. Anal Chem. 2021;93:665–70.

    CAS  PubMed  Google Scholar 

  89. Kuroda K, Yashiro M, Miki Y, et al. Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor. Cancer Sci. 2020;111:4500–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Pituch-Noworolska A, Drabik G, Szatanek R, et al. Immunophenotype of isolated tumour cells in the blood, bone marrow and lymph nodes of patients with gastric cancer. Pol J Pathol. 2006;58:93–7.

    Google Scholar 

  91. Toyoshima K, Hayashi A, Kashiwagi M, et al. Analysis of circulating tumor cells derived from advanced gastric cancer. Int J Cancer. 2015;137:991–8.

    CAS  PubMed  Google Scholar 

  92. Liu G, Neumeister M, Reichensperger J, et al. Therapeutic potential of human adipose stem cells in a cancer stem cell-like gastric cancer cell model. Int J Oncol. 2013;43:1301–9.

    CAS  PubMed  Google Scholar 

  93. Szczepanik A, Sierzega M, Drabik G, et al. CD44(+) cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer. Gastric Cancer. 2019;22:264–72.

    CAS  PubMed  Google Scholar 

  94. Brungs D, Aghmesheh M, Vine KL, et al. Gastric cancer stem cells: evidence, potential markers, and clinical implications. J Gastroenterol. 2016;51:313–26.

    CAS  PubMed  Google Scholar 

  95. Wu X, Qu D, Weygant N, et al. Cancer stem cell marker DCLK1 correlates with tumorigenic immune infiltrates in the colon and gastric adenocarcinoma microenvironments. Cancers (Basel). 2020;12:274.

  96. Wu C, Xie Y, Gao F, et al. Lgr5 expression as stem cell marker in human gastric gland and its relatedness with other putative cancer stem cell markers. Gene. 2013;525:18–25.

    CAS  PubMed  Google Scholar 

  97. Bali P, Lozano-pope I, Pachow C, et al. Early detection of tumor cells in bone marrow and peripheral blood in a fastprogressing gastric cancer model. 2021;58:388–96.

  98. Li TT, Liu H, Li FP, et al. Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response. World J Gastroenterol. 2015;21:13259–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Zhou H, Wang F, Chen H, et al. Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial-mesenchymal transition of gastric cancer. Aging (Albany NY). 2016;8:2023–38.

  100. Chen Y, Li Y, Qi C, et al. Dysregulated KRAS gene-signaling axis and abnormal chromatin remodeling drive therapeutic resistance in heterogeneous-sized circulating tumor cells in gastric cancer patients. Cancer Lett. 2021;517:78–87.

    CAS  PubMed  Google Scholar 

  101. Puisieux A, Brabletz T, Caramel J. Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 2014;16:488–94.

    CAS  PubMed  Google Scholar 

  102. Lu W, Kang Y. Epithelial-mesenchymal plasticity in cancer progression and metastasis. Dev Cell. 2019;49:361–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Lu R, Chen Q, Liu X, et al. Detection of circulating stage III–IV gastric cancer tumor cells based on isolation by size of epithelial tumor: using the circulating tumor cell biopsy technology Transl. Cancer Res. 2019;8:1342–50.

Download references

Acknowledgements

This study was supported by the grants from the Key Program of the Changzhou Commission of Health (ZD2017, to Dr. H Yan), the Major science and technology project of Changzhou Municipal Health Commission (ZD201901, to Dr.J Wu), CSCO foundation (Y-HH202101-0117, to Dr. B Jiang).

Funding

This study was supported by the grants from the Key Program of the Changzhou Commission of Health (ZD2017, to Dr. H Yan), the Major science and technology project of Changzhou Municipal Health Commission (ZD201901, to Dr.J Wu), CSCO foundation (Y-HH202101-0117, to Dr. B Jiang).

Author information

Author notes

  1. Qian Deng and Bo Jiang have contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China

    Qian Deng, Haijiao Yan, Jun Wu & Zhenzhen Cao

  2. Department of Thoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China

    Bo Jiang

Authors
  1. Qian Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haijiao Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenzhen Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QD completed most of the manuscript, ZC and JW participated in the drawing of the diagrams, BJ and HY revised the manuscript.

Corresponding author

Correspondence to Haijiao Yan.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, Q., Jiang, B., Yan, H. et al. Circulating tumor cells in gastric cancer: developments and clinical applications. Clin Exp Med 23, 4385–4399 (2023). https://doi.org/10.1007/s10238-023-01158-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-023-01158-2

Keywords

Search

Navigation