Department of Oncology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, Guangdong Province 528200, China.
Department of Respiration, Foshan Second People's Hospital, Foshan, Guangdong Province 528000, China.
Aging (Albany NY). 2023 Aug 16;15(16):7956-7973. doi: 10.18632/aging.204877.
Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify the relationship between TRGs gene expression and the prognosis of patients with lung adenocarcinoma (LUAD), as well as the prediction of drug treatment efficiency.
A total of 2093 TRGs were acquired from TelNet. The clinical information including age, tumor stage, follow up and outcome (death/survival) and TRGs expression profile of LUAD were obtained from the patients in The Cancer Genome Atlas (TCGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The two databases were used to construct and verify a prognostic model based on the expression of hubTRGs. The tumor mutation burden, immune infiltration and subtypes, as well as IC50 prediction of multiple targeted drugs were also evaluated in TRGs-divided risk groups.
A total of 335 TRGs were significantly differentially expressed in LUAD as compared with normal control. Among them, 9 TRGs (ABCC2, ABCC8, ALDH2, FOXP3, GNMT, JSRP1, MACF1, PLCD3, SULT4A1) were finally identified as hubGenes and used to construct a TRG risk score. The TRG risk score showed favorable performance in constructing a prognostic nomogram in predicting survival of LUAD, and the ROC curves at 1, 3 and 5 years were plotted and the AUROC values were 0.743, 0.754 and 0.735, respectively. Higher TRGs risk score correlated with worse immune subtypes and higher tumor mutation burden in LUAD tissues. In addition, the patients in TRG high risk group harbored a lower TIDE score which indicated potentially better response to immunotherapy.
This study proposed a broad molecular signature of telomere-related genes that can be used in further functional and therapeutic investigations, and also represents an integrated modality for characterizing critical molecules when exploring novel targets for lung cancer immunotherapy.
端粒相关基因（TRGs）在各种类型的肿瘤中起着关键作用。然而，目前缺乏对其在肺癌中的相关性的全面探索。本研究旨在验证 TRGs 基因表达与肺腺癌（LUAD）患者预后的关系，以及预测药物治疗效果。
从 TelNet 中获取了 2093 个 TRGs。从癌症基因组图谱（TCGA）数据库和临床蛋白质组肿瘤分析联盟（CPTAC）数据库中获取了包括年龄、肿瘤分期、随访和结局（死亡/存活）以及 LUAD 的 TRGs 表达谱在内的临床信息。使用这两个数据库构建并验证了基于关键 TRGs 表达的预后模型。还评估了 TRGs 分组风险组中的肿瘤突变负担、免疫浸润和亚型以及多种靶向药物的 IC50 预测。
与正常对照相比，LUAD 中有 335 个 TRGs 表达差异显著。其中，有 9 个 TRGs（ABCC2、ABCC8、ALDH2、FOXP3、GNMT、JSRP1、MACF1、PLCD3、SULT4A1）被最终确定为关键基因，并用于构建 TRG 风险评分。TRG 风险评分在构建预测 LUAD 生存的预后列线图方面表现良好，绘制了 1、3 和 5 年的 ROC 曲线，AUROC 值分别为 0.743、0.754 和 0.735。较高的 TRGs 风险评分与 LUAD 组织中较差的免疫亚型和更高的肿瘤突变负担相关。此外，TRG 高风险组的患者 TIDE 评分较低，这表明对免疫治疗可能有更好的反应。
本研究提出了一个广泛的端粒相关基因分子特征，可用于进一步的功能和治疗研究，也代表了一种综合的方式，用于探索肺癌免疫治疗的新靶点时，对关键分子进行特征描述。
