The number of CD45–CD44+CD54+ cell subsets in peripheral blood of gastric cancer patients and its clinical significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Dongyang ¹ , CHEN Xiaolong ¹ , SONG Xiaohai ¹ , ZHANG Shijiao ² , ZHANG Weihan ¹ , LIU Kai ¹ , HUANG Qiaorong ³ , MENG Wentong ³ , YANG Kun ¹ , CHEN Xinzu ¹ , MO Xianming ³ ,  HU Jiankun ¹

1. Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, Chengdu 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu 610041, P. R. China;
3. Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

HU Jiankun, Email: hujkwch@126.com

Keywords：

gastric cancer; circulating tumor cell; tumor progression

DOI：

10.7507/1007-9424.201912012

Video：

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Objective CD44 and CD54 are two specific biomarkers of gastric cancer stem cells and were used as targets in this study. The number of CD45^–CD44⁺CD54⁺ cell subsets in peripheral blood of gastric cancer patients was detected by flow cytometry. Further, we combined these results with the clinicopathological characteristics of gastric cancer patients to analyze the significance of CD45^–CD44⁺CD54⁺ cell subsets.Methods From December 2016 to September 2017, 38 patients with gastric cancer in gastrointestinal surgery of West China Hospital of Sichuan University were included as the study object. The content of CD45^–CD44⁺CD54⁺ cell subsets in their peripheral blood was detected by flow cytometry and its clinical significance was analyzed.Results The median number of CD45^–CD44⁺CD54⁺ cells were 541.9/mL (71.7–8 057.0/mL) in 38 patients and 555.9/mL (71.7–8 057.0/mL) in the group of patients with R0 resection. Patients without lymph node metastasis were found to have more CD45^–CD44⁺CD54⁺ cells than patients with lymph node metastasis [941.4/mL (183.5–8 057.0)/mL vs 379.3/mL (71.7–2 269.7/mL, P=0.002], and more CD45^–CD44⁺CD54⁺ cells in patients with TNM stage Ⅰ–Ⅱ than in TNM stage Ⅲ–Ⅳ [858.6/mL (183.5–8 057.0/mL) vs 364.6/mL (71.7–2 269.7/mL, P=0.015]. The patients with T3–4 stages (P= 0.025), N⁺ stage (P=0.009) and TNM Ⅲ–Ⅳ stage (P=0.012) had low ratios of the subgroup with high number of CD45^–CD44⁺CD54⁺ cells, respectively. We made a more accurate judgment of N stage and TNM stage when we combined tumor size and the number of CD45^–CD44⁺CD54⁺ cells together. However, there was no significant correlation between the number of CD45^–CD44⁺CD54⁺ cells and other clinicopathological features and prognosis.Conclusions The number of CD45^–CD44⁺CD54⁺ cell subsets is correlated with tumor progression, which might be used to predict TNM stage and N stage. However, the number of patients included in this study is too small, and the clinical significance of CD45^–CD44⁺CD54⁺ subsets in gastric cancer patients needs to be further demonstrated by expanding the sample size.

Citation： ZHANG Dongyang, CHEN Xiaolong, SONG Xiaohai, ZHANG Shijiao, ZHANG Weihan, LIU Kai, HUANG Qiaorong, MENG Wentong, YANG Kun, CHEN Xinzu, MO Xianming, HU Jiankun. The number of CD45^–CD44⁺CD54⁺ cell subsets in peripheral blood of gastric cancer patients and its clinical significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(4): 434-441. doi: 10.7507/1007-9424.201912012 Copy

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2.	Zou K, Yang S, Zheng L, et al. Prognostic role of the circulating tumor cells detected by cytological methods in gastric cancer: a meta-analysis. Biomed Res Int, 2016, 2016: 2765464.
3.	Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov, 2016, 6(5): 479-491.
4.	Sharma S, Zhuang R, Long M, et al. Circulating tumor cell isolation, culture, and downstream molecular analysis. Biotechnol Adv, 2018, 36(4): 1063-1078.
5.	Li TT, Liu H, Yu J, et al. Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells. , 2018, 24(21): 2236-2246.
6.	Ikeguchi M, Kaibara N. Detection of circulating cancer cells after a gastrectomy for gastric cancer. Surg Today, 2005, 35(6): 436-441.
7.	Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell, 2013, 23(5): 573-581.
8.	Eaves CJ. Cancer stem cells: Here, there, everywhere? Nature, 2008, 456(7222): 581-582.
9.	Chen T, Yang K, Yu JH, et al. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res, 2012, 22(1): 248-258.
10.	李晓松. 医学统计学. 第2版. 北京: 高等教育出版社, 2008: 234-238.
11.	Li M, Zhang B, Zhang Z, et al. Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer. Biomed Res Int, 2014, 2014: 981261.
12.	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(12): 3954-3961.
13.	Diao D, Cheng Y, Song Y, et al. D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer. BMC Cancer, 2017, 17(1): 56.
14.	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(1): 171.
15.	Yang C, Zou K, Yuan Z, et al. Prognostic value of circulating tumor cells detected with the cellsearch system in patients with gastric cancer: evidence from a meta-analysis. Onco Targets Ther, 2018, 11: 1013-1023.
16.	Cheng B, Tong G, Wu X, et al. Enumeration and characterization of circulating tumor cells and its application in advanced gastric cancer. Onco Targets Ther, 2019, 12: 7887-7896.
17.	Yang C, Zhang N, Wang S, et al. Wedge-shaped microfluidic chip for circulating tumor cells isolation and its clinical significance in gastric cancer. J Transl Med, 2018, 16(1): 139.
18.	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(2): 235-242.
19.	Abdallah EA, Braun AC, Flores BCTCP, et al. The potential clinical implications of circulating tumor cells and circulating tumor microemboli in gastric cancer. Oncologist, 2019, 24(9): e854-e863.
20.	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(4): e382-e386.
21.	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(2): 1294-1298.
22.	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(26): 6083-6088.
23.	Kolostova K, Matkowski R, Gürlich R, et al. Detection and cultivation of circulating tumor cells in gastric cancer. Cytotechnology, 2016, 68(4): 1095-1102.
24.	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(47): 13259-13267.
25.	Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science, 2013, 339(6119): 580-584.
26.	Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
27.	Jin J, Tang K, Xin Y, et al. Hemodynamic shear flow regulates biophysical characteristics and functions of circulating breast tumor cells reminiscent of brain metastasis. Soft Matter, 2018, 14(47): 9528-9533.
28.	Mitchell MJ, Wayne E, Rana K, et al. TRAIL-coated leukocytes that kill cancer cells in the circulation. Proc Natl Acad Sci U S A, 2014, 111(3): 930-935.
29.	Gül N, Babes L, Siegmund K, et al. Macrophages eliminate circulating tumor cells after monoclonal antibody therapy. J Clin Invest, 2014, 124(2): 812-823.
30.	Watanabe T, Okumura T, Hirano K, et al. Circulating tumor cells expressing cancer stem cell marker CD44 as a diagnostic biomarker in patients with gastric cancer. Oncol Lett, 2017, 13(1): 281-288.
31.	Toyoshima K, Hayashi A, Kashiwagi M, et al. Analysis of circulating tumor cells derived from advanced gastric cancer. Int J Cancer, 2015, 137(4): 991-998.

1. Liu K, Yang K, Zhang WH, et al. Changes of esophagogastric junctional adenocarcinoma and gastroesophageal reflux disease among surgical patients during 1988-2012: a single-institution, high-volume experience in China. Ann Surg, 2016, 263(1): 88-95.
2. Zou K, Yang S, Zheng L, et al. Prognostic role of the circulating tumor cells detected by cytological methods in gastric cancer: a meta-analysis. Biomed Res Int, 2016, 2016: 2765464.
3. Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov, 2016, 6(5): 479-491.
4. Sharma S, Zhuang R, Long M, et al. Circulating tumor cell isolation, culture, and downstream molecular analysis. Biotechnol Adv, 2018, 36(4): 1063-1078.
5. Li TT, Liu H, Yu J, et al. Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells. , 2018, 24(21): 2236-2246.
6. Ikeguchi M, Kaibara N. Detection of circulating cancer cells after a gastrectomy for gastric cancer. Surg Today, 2005, 35(6): 436-441.
7. Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell, 2013, 23(5): 573-581.
8. Eaves CJ. Cancer stem cells: Here, there, everywhere? Nature, 2008, 456(7222): 581-582.
9. Chen T, Yang K, Yu JH, et al. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res, 2012, 22(1): 248-258.
10. 李晓松. 医学统计学. 第2版. 北京: 高等教育出版社, 2008: 234-238.
11. Li M, Zhang B, Zhang Z, et al. Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer. Biomed Res Int, 2014, 2014: 981261.
12. 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(12): 3954-3961.
13. Diao D, Cheng Y, Song Y, et al. D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer. BMC Cancer, 2017, 17(1): 56.
14. 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(1): 171.
15. Yang C, Zou K, Yuan Z, et al. Prognostic value of circulating tumor cells detected with the cellsearch system in patients with gastric cancer: evidence from a meta-analysis. Onco Targets Ther, 2018, 11: 1013-1023.
16. Cheng B, Tong G, Wu X, et al. Enumeration and characterization of circulating tumor cells and its application in advanced gastric cancer. Onco Targets Ther, 2019, 12: 7887-7896.
17. Yang C, Zhang N, Wang S, et al. Wedge-shaped microfluidic chip for circulating tumor cells isolation and its clinical significance in gastric cancer. J Transl Med, 2018, 16(1): 139.
18. 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(2): 235-242.
19. Abdallah EA, Braun AC, Flores BCTCP, et al. The potential clinical implications of circulating tumor cells and circulating tumor microemboli in gastric cancer. Oncologist, 2019, 24(9): e854-e863.
20. 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(4): e382-e386.
21. 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(2): 1294-1298.
22. 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(26): 6083-6088.
23. Kolostova K, Matkowski R, Gürlich R, et al. Detection and cultivation of circulating tumor cells in gastric cancer. Cytotechnology, 2016, 68(4): 1095-1102.
24. 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(47): 13259-13267.
25. Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science, 2013, 339(6119): 580-584.
26. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
27. Jin J, Tang K, Xin Y, et al. Hemodynamic shear flow regulates biophysical characteristics and functions of circulating breast tumor cells reminiscent of brain metastasis. Soft Matter, 2018, 14(47): 9528-9533.
28. Mitchell MJ, Wayne E, Rana K, et al. TRAIL-coated leukocytes that kill cancer cells in the circulation. Proc Natl Acad Sci U S A, 2014, 111(3): 930-935.
29. Gül N, Babes L, Siegmund K, et al. Macrophages eliminate circulating tumor cells after monoclonal antibody therapy. J Clin Invest, 2014, 124(2): 812-823.
30. Watanabe T, Okumura T, Hirano K, et al. Circulating tumor cells expressing cancer stem cell marker CD44 as a diagnostic biomarker in patients with gastric cancer. Oncol Lett, 2017, 13(1): 281-288.
31. Toyoshima K, Hayashi A, Kashiwagi M, et al. Analysis of circulating tumor cells derived from advanced gastric cancer. Int J Cancer, 2015, 137(4): 991-998.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The number of CD45^–CD44⁺CD54⁺ cell subsets in peripheral blood of gastric cancer patients and its clinical significance

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