Li Yilin, Zhang Xiaotian, Gong Jifang, Zhang Qiyue, Gao Jing, Cao Yanshuo, Wang Daisy Dandan, Lin Peter Ping, Shen Lin
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Cytelligen, San Diego, CA 92121, USA.
Chin J Cancer Res. 2016 Dec;28(6):579-588. doi: 10.21147/j.issn.1000-9604.2016.06.04.
Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells (CTCs) correlated with therapeutic efficacy for advanced gastric cancer (AGC) patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients' clinical prognosis.
The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment (SE) and immunostaining-fluorescence hybridization (iFISH) platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.
CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 mL and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival (PFS) and overall survival (OS). In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.
Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
先前的研究表明，循环肿瘤细胞（CTC）中8号染色体非整倍体与晚期胃癌（AGC）患者的治疗效果相关。在对同一AGC患者群体进行的这项随访研究中，我们调查了CTC中8号染色体非整倍体是否以及如何与患者的临床预后相关。
对31例新诊断的AGC患者进行前瞻性研究。应用先前建立的整合消减富集（SE）和免疫染色荧光杂交（iFISH）平台来识别、计数和表征CTC。在治疗前后对患者进行CTC定量及8号染色体非整倍体分析。
93.5%的AGC患者检测到CTC，鉴定出两种具有不同阈值的CTC亚型，阈值为每7.5 mL≥2的多倍体CTC以及阈值为≥4的多倍体加三倍体CTC，发现它们与无进展生存期（PFS）和总生存期（OS）差显著相关。特别是，在初始治疗6周后多倍体CTC增加≥10%的患者PFS和OS较差，而多倍体CTC减少≥10%的患者则观察到PFS和OS改善。在调整临床显著因素后，治疗后多倍体CTC增加≥10%是PFS和OS的唯一独立预测因素。
CTC非整倍体与AGC患者的预后相关。治疗前后多倍体CTC的定量比较监测可能有助于预测预后改善或不良以及化疗耐药性。
