因为在癌症环境中，肿瘤细胞可能使用细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 来逃避免疫系统。本研究旨在鉴定 CTLA-4 相关的长非编码 RNA (lncRNA) 并评估其在肺腺癌 (LUAD) 发展中的作用。临床和基因组数据来自癌症基因组图谱 (TCGA)、MSigDB 和 Gene Weaver。使用Cox回归鉴定CTLA-4相关的基于lncRNA的基因特征（CTLA4LncSigs），建立风险评分模型和独立预后模型。进行富集分析（GO/KEGG）。孟德尔随机化 (MR) 分析研究了氮代谢与肺癌的关系，并用贝叶斯加权 MR (BWMR) 解决了不确定性。探讨了与肿瘤微环境和药物敏感性的相关性。19个CTLA4LncSigs显着影响LUAD预后。风险评分证明了其作为预后因素的独立性。功能分析揭示了 lncRNA 对氮代谢的影响。 MR 和 BWMR 证实了氮代谢途径在肺癌中的保护作用。我们的研究鉴定了与 LUAD 预后相关的 CTLA-4 相关 lncRNA，并揭示了氮代谢途径在对抗 LUAD 发展中先前未被发现的保护作用，为这种侵袭性癌症亚型的潜在治疗靶点和预后生物标志物。© 2024。作者。

Since in the cancer setting, tumor cells may use cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to evade the immune system. This study aimed to identify CTLA-4-related long non-coding RNAs (lncRNAs) and assess their roles in lung adenocarcinoma (LUAD) development.Clinical and genomic data were obtained from The Cancer Genome Atlas (TCGA), MSigDB and Gene Weaver. CTLA-4-related lncRNA-based gene signatures (CTLA4LncSigs) were identified using Cox regression, establishing a risk score model and an independent prognostic model. Enrichment analysis (GO/KEGG) was performed. Mendelian randomization (MR) analysis investigated the nitrogen metabolism and lung cancer relationship, with Bayesian weighted MR (BWMR) addressing uncertainties. Correlations with tumor microenvironment and drug sensitivity were explored.Nineteen CTLA4LncSigs significantly influenced LUAD prognosis. The risk score demonstrated independence as a prognostic factor. Functional analysis revealed lncRNAs' impact on nitrogen metabolism. MR and BWMR confirmed the protective role of the nitrogen metabolism pathway in lung cancer.Our study identifies CTLA-4-related lncRNAs associated with LUAD prognosis and uncovers a previously undiscovered protective role of the nitrogen metabolism pathway in combating LUAD development, providing new insights into potential therapeutic targets and prognostic biomarkers for this aggressive cancer subtype.© 2024. The Author(s).