目的：采用生物信息学方法探索与肾透明细胞癌(ccRCC)组织中铁死亡相关的lncRNA，并探讨其与免疫细胞浸润及患者预后的相关性，为ccRCC 患者提供新的分子靶点。方法：从癌症基因组图谱(TCGA)数据库下载ccRCC 的转录本数据和临床数据，利用单样本基因集富集分析(ssGSEA)及相关性分析获得与铁死亡相关的lncRNA；通过单因素和多因素回归分析构建与铁死亡相关的lncRNA 特征图，分析其与预后的关系；利用R软件分析铁死亡相关lncRNA 与肿瘤免疫细胞浸润和药物敏感性之间的关系。构建铁死亡相关RNA网络，并通过qPCR 验证中国人ccRCC 组织和癌旁组织（取自2019 年12 月至2021 年03 月间在西南医科大学附属医院手术切除8例标本）中关键lncRNA 的表达。结果：Kaplan-Meier 分析表明，铁死亡评分高的患者总OS率低于铁死亡评分低的患者。单因素和多因素回归分析确定11 个ccRCC 铁死亡相关lncRNA 可评估患者预后，并构建ccRCC患者1、3、5 年预后预测列线图。免疫细胞浸润分析表明，铁死亡相关lncRNA 与ccRCC 免疫细胞浸润密切相关，其中LINC01871、PRKAR1B-AS1和CYTOR是调节肿瘤免疫细胞浸润的关键lncRNA。化疗药物敏感性分析表明，高风险患者对甲氨蝶呤、紫杉醇、顺铂和多柔比星更为敏感。构建的包含3 个lncRNA、15 个miRNA 和15 个mRNA的RNA网络中，验证实验显示LINC01871、LINC00472 和CYTOR在ccRCC 组织中显著上调。结论：通过生物信息学方法获得11个与铁死亡相关的lncRNA，证明其与ccRCC组织免疫细胞浸润、化疗药物敏感性和患者预后相关，为探索ccRCC铁死亡相关lncRNA标志物提供重要参考。

Objective: To screen lncRNAs related to ferroptosis in renal clear cell carcinoma (ccRCC) by bioinformatics methods, and to explore their correlation with clinical prognosis and immune cell infiltration, in order to provide new targets for the treatment of ccRCC patients. Methods: Transcript data and clinical data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) database, and ferroptosis-related lncRNAs were obtained using single-sample gene set enrichment analysis (ssGSEA) and correlation analysis. Through univariate and multivariate regression analyses, the characteristics of lncRNAs related to ferroptosis were constructed, and their prognostic value was further analyzed. R software was used to analyze the relationship between the characteristics of ferroptosis-related lncRNAs and tumor immune infiltration and drug sensitivity. A ferroptosis-related ceRNA network was constructed, and the expression of key lncRNAs in Chinese ccRCC tissues and paraneoplastic tissues (samples from 8 cases surgically resected at the Affiliated Hospital of Southwest Medical University between Dec 2019 and Mar 2021) was verified by qPCR. Results: Kaplan-Meier analysis showed that patients with high ferroptosis scores had lower overall survival (OS) than patients with low ferroptosis scores. Univariate and multivariate regression analyses identified 11 ccRCC ferroptosis-related prognostic lncRNAs, and the nomograms for predicting the prognosis of ccRCC patients at 1, 3, and 5 years were constructed. Immune infiltration analysis showed that the characteristics of ferroptosis-related lncRNAs were closely related to ccRCC immune infiltration, among which LINC01871, PRKAR1B-AS1 and CYTOR were the key lncRNAs regulating tumor immune infiltration. Chemotherapy drug sensitivity analysis showed that high-risk patients were more sensitive to methotrexate, paclitaxel, cisplatin, and doxorubicin. Finally, A ceRNA network containing 3 lncRNAs, 15 miRNAs and 15 mRNAs was constructed. qPCR indicated that LINC01871, LINC00472 and CYTOR were significantly up-regulated in ccRCC tissues. Conclusion: Eleven ferroptosis-related lncRNAs were obtained by bioinformatics methods, and they were proved to be related to ccRCC prognosis, immune infiltration and chemotherapeutic drug sensitivity, providing an important reference for exploring ferroptosis-related lncRNA markers in ccRCC.

四川省科研项目（No. LY-105）；西南医科大学青年基金（No. 2018-ZRQN-142）