An aging-related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.
An aging-related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.
复制标题
衰老相关特征可预测肺腺癌的良好结果和免疫原性
DOI：
10.1111/cas.15254
复制
发表时间：
2022-03
期刊：
影响因子：
5.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Zhang W;Li Y;Lyu J;Shi F;Kong Y;Sheng C;Wang S;Wang Q
衰老已被证明在癌症（包括肺腺癌（LUAD））的预后和治疗效果中发挥着至关重要的作用。这项新颖的研究旨在构建一个与衰老相关的风险特征来评估 LUAD 的预后和免疫原性。从 12 个独立队列的总共 2518 名 LUAD 患者中收集了转录组图谱和临床信息。通过将特定基因表达与相应的回归系数相结合来开发风险特征。还使用了一组接受免疫检查点抑制剂（ICI）治疗的队列。随后，基于 21 个衰老相关基因开发了风险特征。低风险评分的 LUAD 患者在发现组和验证组中均表现出改善的生存结果。进一步的免疫学分析显示，低风险亚组中淋巴细胞浸润增加、免疫抑制细胞浸润减少、免疫反应相关途径以及有利的 ICI 预测因子富集。基因组突变探索表明，在具有低风险特征的患者中，TP53、KEAP1、SMARCA4 和 RBM10 等显着驱动基因的突变负担增加且突变率较高。在免疫治疗队列中，观察到低风险衰老评分与延长 ICI 预后显着相关。总体而言，估计的衰老特征被证明能够评估预后、肿瘤微环境和免疫原性，除了促进 LUAD 患者的个体化治疗计划之外，还进一步为制定预后预测和免疫治疗策略提供了线索。衰老相关特征预测肺腺癌的良好结果和免疫原性。
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. Aging‐related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.
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DOI：
10.1016/j.omtn.2020.10.033
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chong W;Wang Z;Shang L;Jia S;Liu J;Fang Z;Du F;Wu H;Liu Y;Chen Y;Chen H
通讯作者：
Chen H
肌联蛋白突变与实体瘤检查点阻断的反应相关
影响因子：
8
作者：
Jia, Qingzhu;Wang, Jun;Zhu, Bo
通讯作者：
Zhu, Bo
DOI：
10.1073/pnas.2023216118
发表时间：
2021-08-17
影响因子：
11.1
作者：
Huang Z;Chen B;Liu X;Li H;Xie L;Gao Y;Duan R;Li Z;Zhang J;Zheng Y;Su W
通讯作者：
Su W
影响因子：
11.5
作者：
Dong, Zhong-Yi;Zhong, Wen-Zhao;Wu, Yi-Long
通讯作者：
Wu, Yi-Long
DOI：
10.1093/gerona/glu166
发表时间：
2015-01-01
影响因子：
5.1
作者：
Broer, Linda;Buchman, Aron S.;Murabito, Joanne M.
通讯作者：
Murabito, Joanne M.