Cui Yankang, Zhang Shaobo, Miao Chenkui, Liang Chao, Chen Xiaochao, Yan Tao, Bu Hengtao, Dong Huiyu, Li Junchen, Li Jie, Wang Zengjun, Liu Bianjiang
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Transl Androl Urol. 2021 Aug;10(8):3317-3331. doi: 10.21037/tau-21-278.
Studies over the past decade have shown that long non-coding RNAs (lncRNAs) play an essential role in the tumorigenesis and progression of kidney renal clear cell carcinoma (KIRC). Meanwhile, autophagy has been demonstrated to regulate KIRC pathogenesis and targeting therapy resistance. However, the prognostic value of autophagy-related lncRNAs in KIRC patients has not been reported before.
In this study, we obtained transcriptome data of 611 KIRC cases from the TCGA database and 258 autophagy-related mRNAs from the HADb database to identify autophagy-related lncRNAs by co-expression network. A prognostic model was then established basing on these autophagy-related lncRNAs, dividing patients into high-risk and low-risk groups. Survival analysis, clinical variables dependent receiver operating characteristic (ROC) analyses, univariate/multivariate Cox analyses, and clinical correlation analysis were performed based on risk signature with R language. Gene set enrichment analysis (GSEA) was then performed to investigate the potential mechanism of the risk signature promoting KIRC progression with GSEA software. CIBERSORT algorithm was performed to assess the impact of these lncRNAs on the infiltration of immune cells.
A total of 17 lncRNAs were screened out and all these lncRNAs were found significantly related to KIRC patients' overall survival in subsequent survival analyses. Besides, the overall survival time in the high-risk group was much poorer than in the low-risk group. The ROC analysis revealed that the prognostic value of risk signature was better than age, gender, grade, and N stage. Univariate/multivariate analyses suggested that the risk signature was an independent predictive factor for KIRC patients. Immune and autophagy related pathways were dramatically enriched in high-risk and low-risk groups, respectively, and lncRNAs related immune cells were identified by CIBERSORT.
In summary, our identified 17 autophagy-related lncRNAs had prognostic value for KIRC patients which may function in immunomodulation.
过去十年的研究表明，长链非编码RNA（lncRNAs）在肾透明细胞癌（KIRC）的肿瘤发生和进展中起重要作用。同时，自噬已被证明可调节KIRC的发病机制和靶向治疗耐药性。然而，自噬相关lncRNAs在KIRC患者中的预后价值此前尚未见报道。
在本研究中，我们从TCGA数据库获取了611例KIRC病例的转录组数据，并从HADb数据库获取了258个自噬相关的mRNA，通过共表达网络鉴定自噬相关lncRNAs。然后基于这些自噬相关lncRNAs建立预后模型，将患者分为高危组和低危组。使用R语言基于风险特征进行生存分析、临床变量依赖的受试者工作特征（ROC）分析、单因素/多因素Cox分析以及临床相关性分析。随后使用GSEA软件进行基因集富集分析，以研究风险特征促进KIRC进展的潜在机制。使用CIBERSORT算法评估这些lncRNAs对免疫细胞浸润的影响。
共筛选出17个lncRNAs，在随后的生存分析中发现所有这些lncRNAs均与KIRC患者的总生存期显著相关。此外，高危组的总生存时间比低危组差得多。ROC分析显示，风险特征的预后价值优于年龄、性别、分级和N分期。单因素/多因素分析表明，风险特征是KIRC患者的独立预测因素。免疫和自噬相关途径分别在高危组和低危组中显著富集，并且通过CIBERSORT鉴定了与免疫细胞相关的lncRNAs。
总之，我们鉴定出的17个自噬相关lncRNAs对KIRC患者具有预后价值，可能在免疫调节中发挥作用。
