Chen Linbao, Wang Chao, Wang Yuning, Hong Tianyu, Zhang Guangwen, Cui Xingang
Department of Urinary Surgery, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), Yinchuan, China.
Ningxia Medical University, Yinchuan, China.
Front Oncol. 2022 Mar 11;11:697697. doi: 10.3389/fonc.2021.697697. eCollection 2021.
Ferroptosis is a cell death process discovered in recent years, highly related to cancer, acute kidney injury, and other diseases. In this study, a pan-renal cancer analysis of ferroptosis-associated genes in renal cancer was performed to construct a multigene joint signature for predicting prognosis in renal cancer patients. First, gene expression profiles were downloaded from the TCGA and GTEx databases to search for genes significantly associated with renal cancer prognosis through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis. Thereafter, the gene-set enrichment analysis (GSEA) was used to identify the biological processes in which ferroptosis-associated genes might be involved. Weighted gene co-expression network analysis resulted in 4,434 differentially expressed genes (DEGs) and 42 co-expression modules, among which ferroptosis-related genes were distributed in 11 gene modules. The survival analysis screening resulted in three DEGs associated with renal cancer prognosis, namely SLC7A11, HMOX1, and MT1G. Specifically, SLC7A11 and HMOX1 were upregulated in renal cancer tissues, while MT1G was downregulated. Receiver operating characteristic (ROC) curves, combined with Kaplan-Meier and Cox regression analysis, revealed that high expression of SLC7A11 was a prognostic risk factor for four different renal cancers, that low expression of HMOX1 was a poor prognostic marker for patients, and that increased expression of MT1G increased the prognostic risk for three additional classes of renal cancer patients, except for renal papillary cell carcinoma. The GSEA results showed that the ferroptosis-related genes from these screens were mainly associated with signaling pathways related to tumor progression and tumor immunity. This study provides potential biological markers for prognosis prediction in renal cancer patients with different subtypes, and these results imply that ferroptosis is highly associated with renal carcinogenesis progression.
铁死亡是近年来发现的一种细胞死亡过程，与癌症、急性肾损伤等疾病高度相关。在本研究中，对肾癌中铁死亡相关基因进行了全肾癌分析，以构建用于预测肾癌患者预后的多基因联合特征。首先，从TCGA和GTEx数据库下载基因表达谱，通过差异基因表达分析、加权基因共表达网络分析（WGCNA）和生存分析来寻找与肾癌预后显著相关的基因。此后，使用基因集富集分析（GSEA）来确定铁死亡相关基因可能参与的生物学过程。加权基因共表达网络分析产生了4434个差异表达基因（DEG）和42个共表达模块，其中铁死亡相关基因分布在11个基因模块中。生存分析筛选出三个与肾癌预后相关的DEG，即SLC7A11、HMOX1和MT1G。具体而言，SLC7A11和HMOX1在肾癌组织中上调，而MT1G下调。受试者工作特征（ROC）曲线结合Kaplan-Meier和Cox回归分析表明，SLC7A11的高表达是四种不同肾癌的预后危险因素，HMOX1的低表达是患者预后不良的标志物，MT1G表达增加增加了除肾乳头状细胞癌外的另外三类肾癌患者的预后风险。GSEA结果表明，这些筛选出的铁死亡相关基因主要与肿瘤进展和肿瘤免疫相关的信号通路有关。本研究为不同亚型肾癌患者的预后预测提供了潜在的生物标志物，这些结果表明铁死亡与肾癌发生发展高度相关。
