Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang, China.
Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Cancer Sci. 2022 Mar;113(3):891-903. doi: 10.1111/cas.15254. Epub 2022 Jan 7.
Aging has been demonstrated to play vital roles in the prognosis and treatment efficacy of cancers, including lung adenocarcinoma (LUAD). This novel study aimed to construct an aging-related risk signature to evaluate the prognosis and immunogenicity of LUAD. Transcriptomic profiles and clinical information were collected from a total of 2518 LUAD patients from 12 independent cohorts. The risk signature was developed by combining specific gene expression with the corresponding regression coefficients. One cohort treated with the immune checkpoint inhibitor (ICI) was also used. Subsequently, a risk signature was developed based on 21 aging-related genes. LUAD patients with low-risk scores exhibited improved survival outcomes in both the discovery and validation cohorts. Further immunology analysis revealed elevated lymphocyte infiltration, decreased infiltration of immune-suppressive cells, immune response-related pathways, and favorable ICI predictor enrichment in the low-risk subgroup. Genomic mutation exploration indicated the enhanced mutation burden and higher mutation rates in significantly driver genes of TP53, KEAP1, SMARCA4, and RBM10 were enriched in patients with a low-risk signature. In the immunotherapeutic cohort, it was observed that low-risk aging scores were markedly associated with prolonged ICI prognosis. Overall, the estimated aging signature proved capable of evaluating the prognosis, tumor microenvironment, and immunogenicity, which further provided clues for tailoring prognosis prediction and immunotherapy strategies, apart from promoting individualized treatment plans for LUAD patients.
衰老是影响癌症预后和治疗效果的关键因素,包括肺腺癌(LUAD)。本研究旨在构建一个与衰老相关的风险特征,以评估 LUAD 的预后和免疫原性。从 12 个独立队列的总共 2518 例 LUAD 患者中收集转录组谱和临床信息。通过结合特定基因表达和相应的回归系数来开发风险特征。还使用了一个接受免疫检查点抑制剂(ICI)治疗的队列。随后,基于 21 个与衰老相关的基因开发了一个风险特征。在发现和验证队列中,低风险评分的 LUAD 患者的生存结果得到改善。进一步的免疫组学分析显示,低风险亚组中淋巴细胞浸润增加,免疫抑制细胞浸润减少,免疫反应相关途径增加,ICI 预测因子富集。基因组突变探索表明,TP53、KEAP1、SMARCA4 和 RBM10 等重要驱动基因的突变负担增强,突变率更高。在免疫治疗队列中,低风险衰老评分与 ICI 预后的延长显著相关。总的来说,该评估衰老特征的方法能够评估预后、肿瘤微环境和免疫原性,为 LUAD 患者的预后预测和免疫治疗策略的制定提供了线索,同时也促进了个体化治疗计划。