进展期胃癌SOX新辅助化疗敏感性相关基因及信号通路的生物信息学分析

目的:探讨与进展期胃癌对替吉奥胶囊联合奥沙利铂(SOX)新辅助化疗敏感性有关的基因及信号通路。方法:收集15例III期胃癌患者术后标本,其中6例SOX新辅助化疗后缓解(缓解组)、6例SOX新辅助化疗后未缓解(未缓解组),3例未行新辅助化疗(未化疗组),在用高通量基因芯片法检测各组标本基因表达谱后,以DNA损伤修复和叶酸代谢方面为重点分析对象,用系统性生物信息学技术筛选出差异基因,并通过KEGG来解释每个差异表达基因所在通路。结果:3组标本的基因表达谱存在明显差异。缓解组与未缓解组间的差异基因主要集中在细胞因子相互作用和NK细胞介导的细胞毒性作用通路上。与未缓解组比较,缓解组与DNA损伤修复相关的3个基因(HUS1、RECQL5、XRCC4)明显上调和1个基因(GADD45G)明显下调;3组间在叶酸代谢方面未找到任何差异基因。结论:影响进展期胃癌SOX新辅助化疗敏感性的基因可能与免疫信号传导有关,相关的基因检测对评估胃癌SOX新辅助化疗效果有一定的意义。

Bioinformatics analysis of genes and signaling pathways associated with sensitivity of advanced gastric cancer to SOX neoadjuvant chemotherapy

Objective: To investigate the genes and signaling pathways associated with the sensitivity of advanced gastric cancer to S-1 plus oxaliplatin (SOX) neoadjuvant chemotherapy.Methods: The surgical specimens from 15 patients with stage III gastric cancer were collected, in which, 6 cases responded (responder group) and 6 cases did not respond (non-responder group) after SOX neoadjuvant chemotherapy, and 3 cases did not receive any neoadjuvant chemotherapy (non-chemotherapy group). After the gene expression profile in each group was detected by high-throughput gene microarray screening, choosing DNA damage repair and folate metabolism as two major analytical aspects, the differentially expressed genes were screened by systemic bioinformatics analysis, and then, pathways associated with the differentially expressed genes were identified through KEGG mapping.Results: There was an obvious different gene expression profiles among the three groups of specimens. The differentially expressed genes between responder group and non-responder group were highly enriched in pathways relevant for cytokine-cytokine interactions and cytotoxicity mediated by NK cells. Of the genes associated with DNA damage repair, three (HUS1, RECQL5 and XRCC4) were up-regulated and one (GADD45G) was down-regulated significantly in responder group compared with non-responder group; no differentially expressed gene related to folate metabolism was found among the three groups.Conclusion: The genes affecting the sensitivity of advanced gastric cancer to SOX neoadjuvant chemotherapy may be associated with immune signal transduction, and the detection of the relevant genes may have certain significance for estimating the efficacy of SOX neoadjuvant chemotherapy for gastric cancer.