基于TCGA数据库筛选和鉴定肺腺癌免疫治疗临床获益关键基因

齐晓光; 祁春艳; 秦博宇; 胡毅; 韩为东

doi:10.3971/j.issn.1000-8578.2020.20.0115

基于TCGA数据库筛选和鉴定肺腺癌免疫治疗临床获益关键基因

Screening and Identification of Key Genes for Clinical Benefit of Immunotherapy on Lung Adenocarcinoma Based on TCGA Database

摘要

摘要:
目的基于全基因组测序分析，探索影响肺腺癌免疫疗效预测的关键基因及其可能的机制。
方法选取癌症基因组图谱中肺腺癌数据集（MSKCC, Science 2015）为研究对象，根据免疫治疗疗效持续时间分为两组：持久临床获益组（durable clinical benefit, DCB）和非持久临床获益组（non-durable clinical benefit, Non-DCB）。分析两组之间基因突变谱的差异，进而探索影响肺腺癌免疫治疗的关键分子及潜在生物学功能。
结果基因突变谱在DCB组和Non-DCB组之间存在差异；进一步对DCB组基因突变谱研究，这些基因主要参与了Ca²⁺通道、Rap1、PI3K-Akt等相关信号通路；蛋白互作网络分析中，筛选出6个节点度最高的核心基因KRAS、PPP2CB、CDC20、DYNCLI2、BRCA1、AKAP9，其中CDC20、BRCA1等基因与肺腺癌患者预后相关。
结论 DCB组涉及的关键核心基因有可能指导肺腺癌的免疫特征分型，对于更加精准的免疫治疗具有重要意义。CDC20和BRCA1有可能成为肺腺癌免疫治疗中潜在的治疗靶点。

Abstract:
Objective To identify key biomarkers for predicting the response to immunotherapy and elucidate the possible underlying mechanism in lung adenocarcinoma based on whole-genome sequencing.
Methods Data set of MSKCC (Science 2015) with lung adenocarcinoma from TCGA database were downloaded. According to the duration time of response to immunotherapy, two groups were divided: durable clinical benefit (DCB) group and non-durable clinical benefit (Non-DCB) group. The differences in gene mutation spectrum between the two groups were analyzed. The key genes and underlying biological functions of immunotherapy for lung adenocarcinoma were further analyzed.
Results There were differences in gene mutation spectrum between the DCB group and the Non-DCB group. In the DCB group, these key genes were mainly involved in Ca signaling pathway, Rap1 and PI3K-AKT pathways. The top 6 hub genes (KRAS, PPP2CB, CDC20, DYNC1I2, BRCA1 and AKAP9) were screened using the PPI network analysis. CDC20 and BRCA1 were associated with the prognosis of lung adenocarcinoma patients.
Conclusion The hub genes involved in the DCB group might be important to guide the classification of immune signature and improve precision immunotherapy for lung adenocarcinoma. In addition, CDC20 and BRCA1 might be potential therapeutic targets for immunotherapy of lung adenocarcinoma.

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