Zhou Fei, Zhu Meiling, Wang Mengyun, Qiu Lixin, Cheng Lei, Jia Ming, Xiang Jiaqing, Wei Qingyi
Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.
J Transl Med. 2016 May 31;14(1):154. doi: 10.1186/s12967-016-0903-z.
Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).
The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.
We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.
SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.
对于接受手术切除的食管鳞状细胞癌（ESCC）患者，辅助化疗在改善总生存期（OS）方面的作用尚不明确，因此存在争议。核苷酸切除修复（NER）可去除铂类化疗诱导的肿瘤细胞中的DNA加合物，从而可能调节治疗效果。本研究评估NER基因的单核苷酸多态性（SNP）是否为接受铂类辅助化疗（PAC）的ESCC患者的预后生物标志物。
分析纳入572例患者，采用TaqMan分析检测NER基因的6个SNP [即XPC（rs1870134和rs2228001）、ERCC2/XPD rs238406和ERCC5/XPG（rs2094258、rs2296147和rs873601）]。采用Kaplan-Meier分析和Cox比例风险模型评估这些接受PAC的ESCC患者的无病生存期（DFS）和OS与上述SNP的相关性。采用受试者工作特征曲线分析评估风险基因型在DFS和OS中的作用。
我们发现，ERCC5/XPG rs2094258和rs873601以及ERCC2/XPD rs238406的SNP与ESCC患者较差的DFS和OS独立相关[ERCC5/XPG rs2094258：CT + TT与CC相比：DFS的调整风险比（adjHR）= 1.68，P = 0.012；OS的adjHR = 1.99，P = 0.0001；ERCC5/XPG rs873601：GA + GG与AA相比：DFS的adjHR = 1.59，P = 0.024；OS的adjHR = 1.91，P = 0.0005；ERCC2/XPD rs238406：TT与GG + GT相比：DFS的adjHR = 1.43，P = 0.020；OS的adjHR = 1.52，P = 0.008]。在综合分析中，随着风险基因型数量的增加，这些风险比也增加。将风险基因型与临床特征或TNM分期系统相结合的模型在预测接受PAC的ESCC患者的预后方面表现更佳。
在本研究人群中，ERCC2/XPD和ERCC5/XPG的SNP可能独立且联合预测接受PAC的ESCC患者的生存情况。有必要在其他研究人群中进行进一步验证。
Zotero 插件