Zheng Xiumei, Fan Li, Zhou Pengfei, Ma Hong, Huang Shaoyi, Yu Dandan, Zhao Lei, Yang Shengli, Liu Jun, Huang Ai, Cai Congli, Dai Xiaomeng, Zhang Tao
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, China.
Wuhan YZY Medical Science & Technology Co., Ltd., biolake, No.666 Gaoxin Road, Wuhan, China.
Transl Oncol. 2017 Jun;10(3):431-441. doi: 10.1016/j.tranon.2017.02.007. Epub 2017 Apr 25.
Gastric cancer studies indicated a potential correlation between circulating tumor cells (CTCs) in peripheral blood and tumor relapse/metastasis. The prevalence and significance of circulating tumor microemboli (CTM) in gastric cancer remain unknown. We investigated the prevalence and prognostic value of CTCs and CTM for progression-free survival (PFS) and overall survival (OS) in gastric cancer patients.
Eighty-one gastric cancer patients consented to provide 5ml of peripheral blood before systematic therapy. CTCs and CTM were isolated using isolation by size of epithelial tumor cells and characterized by cytopathologists. For 41 stage IV gastric cancer patients, CTM was investigated as a potential biomarker to predict prognosis.
CTCs were detected in 51 patients; the average count was 1.81. In clinical stage I, II, III, and IV patients, the average CTC counts were 1.40, 0.67, 1.24, and 2.71, respectively. CTM were detected in 3 of 33 clinical stage I to IIIb patients, at an average of 0.12 (0-2). CTM were detected in 13 of 53 clinical stage IIIc to IV patients, at an average of 1.26 (0-22). In stage IV patients, CTM positivity correlated with the CA125 level. PFS and OS in CTM-positive patients were significantly lower than in CTM-negative patients (P<.001). CTM positivity was an independent factor for determining the PFS (P=.016) and OS (P=.003) of stage IV patients in multivariate analysis. Using markers of the epithelial-mesenchymal transition, single CTCs were divided into three phenotypes including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs. For CTM, CK-/Vimentin+/CD45- and CK+/Vimentin+/CD45- phenotypes were observed, but the CK+/Vimentin-/CD45- CTM phenotype was not. CA125 was detected in gastric cancer cell lines BGC823 and MGC803.
In stage IV patients, CTM positivity was correlated with serum CA125 level. CTM were an independent predictor of shorter PFS and OS in stage IV patients. Thus, CTM detection may be a useful tool to predict prognosis in stage IV patients.
胃癌研究表明外周血循环肿瘤细胞（CTC）与肿瘤复发/转移之间可能存在关联。胃癌中循环肿瘤微栓子（CTM）的发生率及意义尚不清楚。我们研究了CTC和CTM对胃癌患者无进展生存期（PFS）和总生存期（OS）的发生率及预后价值。
81例胃癌患者同意在系统治疗前提供5ml外周血。采用上皮肿瘤细胞大小分离法分离CTC和CTM，并由细胞病理学家进行特征描述。对于41例IV期胃癌患者，研究CTM作为预测预后的潜在生物标志物。
51例患者检测到CTC；平均计数为1.81。在临床I、II、III和IV期患者中，平均CTC计数分别为1.40、0.67、1.24和2.71。33例临床I至IIIb期患者中有3例检测到CTM，平均为0.12（0 - 2）。53例临床IIIc至IV期患者中有13例检测到CTM，平均为1.26（0 - 22）。在IV期患者中，CTM阳性与CA125水平相关。CTM阳性患者的PFS和OS显著低于CTM阴性患者（P <.001）。在多因素分析中，CTM阳性是决定IV期患者PFS（P =.016）和OS（P =.003）的独立因素。使用上皮-间质转化标志物，单个CTC分为三种表型，包括上皮性CTC、双表型上皮/间质CTC和间质性CTC。对于CTM，观察到CK - /波形蛋白 + /CD45 - 和CK + /波形蛋白 + /CD45 - 表型，但未观察到CK + /波形蛋白 - /CD45 - CTM表型。在胃癌细胞系BGC823和MGC803中检测到CA125。
在IV期患者中，CTM阳性与血清CA125水平相关。CTM是IV期患者PFS和OS缩短的独立预测因素。因此，CTM检测可能是预测IV期患者预后的有用工具。
