Detection and clinical significance of circulating tumor cells in patients with gastric cancer
-
摘要:
目的 探讨胃癌患者外周血中循环肿瘤细胞的临床意义。 方法 采集45例胃癌患者的外周血,应用密度梯度离心法和免疫荧光法检测外周血中的循环肿瘤细胞(circulating tumor cells,CTCs),并比较其临床病理意义。 结果 应用密度梯度离心法和免疫荧光法检测胃癌患者外周血中的CK19阳性肿瘤细胞即为CTCs。45例胃癌患者中27例为CTCs阳性,CTCs阳性与淋巴结转移(P=0.007)、远处转移(P=0.035)和复发密切相关(P=0.035),而与性别、年龄、肿瘤部位和TNM分期、肿瘤分化程度无关(P> 0.05)。 结论 CTCs与胃癌的不良预后相关。 Abstract:Objective To detect circulating tumor cells (CTCs) in patients with gastric cancer and evaluate the relationship among CTCs, clinico-pathological characteristics, and prognosis of gastric cancer. Methods Peripheral blood samples (10 mL in EDTA) were obtained from 45 patients with gastric cancer. CTCs were detected using density-gradient centrifugation and immunofluorescence staining. The clinical significance of the two methods were also compared and investigated. Results CTC-positive case was defined by the presence of at least one CK19 (+)-CTC per 10 mL of the sample. CTCs were found in 27 of the 45 patients with gastric cancer. The presence of CTCs was significantly correlated with lymph node metastasis, distant metastasis, and recurrence (P=0.007, 0.035, 0.035, respectively). However, CTCs were not significantly correlated with sex, age, tumor location, TNM staging, and tumor differentiation (P>0.05). Conclusion CTCs were associated with poor prognosis of gastric cancer. -
Key words:
- gastric cancer /
- circulating tumor cells /
- CK19 /
- recurrence /
- density gradient centrifugation
-
表 1 胃癌患者不同临床病理特征与CTCs阳性率的相关性
Table 1. Correlation between clinicopathological features and positive rates of CTCs in patients with gastric cancer
-
[1] Yu M, Stott S, Toner M, et al. Circulating tumor cells: approaches to isolation and characterization[J]. J Cell Biol, 2011, 192(3):373-382. doi: 10.1083/jcb.201010021 [2] Lianidou ES, Markou A. Circulating tumor cells in breast cancer: Detection systems, molecular characterization, and future challenges[J]. Clin Chem, 2011, 57(9):1242-1255. doi: 10.1373/clinchem.2011.165068 [3] Paterlini-Brechot P, Benali NL. Circulating tumor cells (CTC) detection: clinical impact and future directions[J]. Cancer Lett, 2007, 253(2):180-204. doi: 10.1016/j.canlet.2006.12.014 [4] Maheswaran S, Haber DA. Circulating tumor cells: a window into cancer biology and metastasis[J]. Curr Opin Genet Dev, 2010, 20 (1): 96-99. doi: 10.1016/j.gde.2009.12.002 [5] Cristofanilli M, Hayes DF, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer[J]. J Clin Oncol, 2005, 23(7):1420-1430. doi: 10.1200/JCO.2005.08.140 [6] Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival[J]. Clin Cancer Res, 2006, 129(14Pt1):4218-4224. http://www.tandfonline.com/servlet/linkout?suffix=CIT0120&dbid=8&doi=10.1586%2F14737159.2015.1110021&key=16857794 [7] Weissenstein U, Schumann A, Reif M, et al. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies[J]. BMC Cancer, 2012, 12:206. doi: 10.1186/1471-2407-12-206 [8] Hong B, Zu Y. Detecting circulating tumor cells: current challenges and new trends[J]. Theranostics, 2013, 3(6):377-394. doi: 10.7150/thno.5195 [9] Alix-Panabières C, Pantel K. Circulating tumor cells: liquid biopsy of cancer[J]. Clin Chem, 2013, 59(1):110-118. http://europepmc.org/abstract/MED/24445939 [10] Nagrath S, Sequist LV, Maheswaran S, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology[J]. Nature, 2007, 450(7173):1235- 1239. doi: 10.1038/nature06385 [11] Pecot CV, Bischoff FZ, Mayer JA, et al. A novel platform for detection of CK+ and CK- ctcs[J]. Cancer Discov, 2011, 1(7):580-586. doi: 10.1158/2159-8290.CD-11-0215 [12] Krebs MG, Sloane R, Priest L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non small-cell-lung cancer[J]. J Clin Oncol, 2011, 29(12):1556-1563. doi: 10.1200/JCO.2010.28.7045 [13] Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor respose, progression-free survival, and overall survival in patients with metastatic colorectal cancer[J]. J Clin Oncol, 2008, 26(19):3213-3221. doi: 10.1200/JCO.2007.15.8923 [14] Rahbari NN, Aigner M, Thorlund K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer[J]. Gastroenterology, 2010, 138(5):1714-1726. doi: 10.1053/j.gastro.2010.01.008 [15] 李熳, 刘霞, 张志广, 等.缺氧影响胃腺癌循环肿瘤细胞发生的体内实验研究[J].中华消化杂志, 2014, 34(3):156-160. doi: 10.3760/cma.j.issn.0254-1432.2014.03.004Li M, Liu X, Zhang ZG, et al. Experiments in vivo of the impact of hypoxia on circulating tumor cells in gastric adenocarcinoma[J]. Chinese Joumal of Digestion, 2014, 34(3):156-160. doi: 10.3760/cma.j.issn.0254-1432.2014.03.004