Department of Oncological & Surgical Sciences, Section of Clinica Chirurgica 2, University of Padova, via Giustiniani 2, 35128, Padua, Italy.
J Transl Med. 2009 Dec 22;7:111. doi: 10.1186/1479-5876-7-111.
The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma.
Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5).
Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome.
Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.
循环肿瘤细胞（CTC）的检测被认为是提高实体瘤患者风险分层的有前途的工具。我们研究了 CTC 相关基因的表达是否为胃癌患者的 TNM 分期系统增加了任何预后价值。
回顾性纳入 70 例 TNM 分期 I 至 IV 期胃癌患者。通过定量实时 PCR（qrtPCR）检测外周血样本中四个 CTC 相关基因：癌胚抗原（CEA）、细胞角蛋白 19（CK19）、血管内皮生长因子（VEGF）和 Survivin（BIRC5）的表达。
Survivin、CK19、CEA 和 VEGF 的基因表达在 98.6%、97.1%、42.9%和 38.6%的病例中均高于正常对照，提示 Survivin 和 CK19 具有潜在的诊断价值。多变量生存分析表明，TNM 分期和 Survivin mRNA 水平是独立的预后因素，表明外周血中 Survivin 的表达为 TNM 系统增加了预后信息。与之前发表的数据相反，CEA、CK19 和 VEGF 的转录丰度与患者的临床结局无关。
Survivin 的基因表达水平为当前的 TNM 分期系统增加了显著的预后价值。在更大的前瞻性和多中心系列中验证这些发现可能导致该生物标志物在常规临床实践中的实施，以优化风险分层，并最终为这些患者的个体化治疗管理提供依据。
