端粒相关基因（TRGs）在各种类型的肿瘤中起着关键作用。然而，在肺癌中，对其相关性缺乏全面的探索。该研究旨在验证TRGs基因表达与肺腺癌（LUAD）患者预后以及药物治疗效果的关系。从TelNet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、随访和结果（死亡/存活）以及LUAD的TRGs表达谱的临床信息。使用这两个数据库构建和验证了基于关键TRGs表达的预后模型。在TRGs分组的风险组中，还评估了肿瘤突变负荷、免疫浸润和亚型以及多靶向药物的IC50预测。与正常对照相比，共有335个TRGs在LUAD中表达有显著差异。其中，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LUAD预后图谱中显示出良好的性能，绘制的1年、3年和5年的ROC曲线的AUROC值分别为0.743、0.754和0.735。更高的TRGs风险评分与LUAD组织中的更差的免疫亚型和更高的肿瘤突变负荷相关。此外，TRG高风险组的患者具有较低的TIDE评分，表明对免疫治疗可能有更好的反应。本研究提出了一种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，并且代表了一种综合模式，用于表征探索肺癌免疫治疗新靶点的关键分子。

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.