Zhang Xianlu, Hu Jiyuan, Zheng Haoyuan, Ren Jiayi, Mu Siyu, Chen Yiming, Song Guoli, Chen Ya-Ang, Zhang Gejun
Department of Urology Surgery, The First Affiliation Hospital of China Medical University, Shenyang, 110000, Liaoning, China.
Institute of Urology, China Medical University, Shenyang, 110000, Liaoning, China.
Sci Rep. 2024 Dec 28;14(1):31460. doi: 10.1038/s41598-024-83263-0.
To evaluate the predictive utility of N6-methyladenosine (m6A)-associated long non-coding RNAs (lncRNAs) for the prognosis and immunotherapy response in papillary renal cell carcinoma (pRCC). Transcriptomic data of pRCC samples were extracted from the TCGA database. The m6A-related lncRNAs were identified by Pearson correlation analysis. Univariate and LASSO regression analyses were used to develop a risk model. The discrimination and predictive ability were evaluated through survival analysis, ROC analysis and consensus clustering. Tumor mutation burden (TMB) and immune infiltration of the risk groups were compared. A prognostic nomogram was constructed using six m6A-related lncRNAs, and validated through calibration and decision curve analysis (DCA). The lncRNAs HCG25 and NOP14-AS1 were knocked down in a human pRCC cell line using specific siRNA constructs, and the proliferation and migration rates were assessed by the CCK-8 and transwell assays. We identified a total of 153 m6A-related lncRNAs in pRCC datasets, of which six were selected for constructing a m6A-related lncRNA pRCC prognostic model. Mutations in the SETD2 gene correlated with worse prognosis. Significant differences were observed in immune cell infiltration between the two risk groups. A clinical prognostic nomogram for pRCC was further established based on clinical variables. In vitro assays further showed that HCG25 and NOP14-AS1 regulate the proliferation and migration of pRCC cells. The results validated the discrimination ability of both the m6A-related lncRNA pRCC prognostic model and the pRCC clinical prognostic nomogram. We developed a clinical prognostic nomogram for pRCC using pRCC prognostic-associated m6A-related lncRNAs, which can be utilized for predicting the prognosis and immune landscape of pRCC patients.
评估N6-甲基腺苷（m6A）相关长链非编码RNA（lncRNA）对乳头状肾细胞癌（pRCC）预后及免疫治疗反应的预测效用。从TCGA数据库中提取pRCC样本的转录组数据。通过Pearson相关分析鉴定m6A相关lncRNA。采用单因素和LASSO回归分析建立风险模型。通过生存分析、ROC分析和一致性聚类评估判别能力和预测能力。比较风险组的肿瘤突变负荷（TMB）和免疫浸润情况。使用6个m6A相关lncRNA构建预后列线图，并通过校准和决策曲线分析（DCA）进行验证。使用特异性siRNA构建体在人pRCC细胞系中敲低lncRNA HCG25和NOP14-AS1，并通过CCK-8和transwell试验评估增殖和迁移率。我们在pRCC数据集中共鉴定出153个m6A相关lncRNA，其中6个被选用于构建m6A相关lncRNA pRCC预后模型。SETD2基因的突变与较差的预后相关。两个风险组之间在免疫细胞浸润方面观察到显著差异。基于临床变量进一步建立了pRCC的临床预后列线图。体外试验进一步表明，HCG25和NOP14-AS1调节pRCC细胞的增殖和迁移。结果验证了m6A相关lncRNA pRCC预后模型和pRCC临床预后列线图的判别能力。我们使用与pRCC预后相关的m6A相关lncRNA开发了一种pRCC临床预后列线图，可用于预测pRCC患者的预后和免疫格局。
