Abstract
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.
Highlights
Renal cancer is a large heterogeneous group of cancers derived from renal tubular cells, and, as the seventh most common malignancy worldwide, the incidence is still increasing [1]
Ferroptosis is a cell death modality mainly driven by lipid peroxidation [17]
When cellular ROS accumulate over the amount of redox required for GSH and phospholipid hydroperoxides, redox homeostasis is disrupted, triggering ferroptosis cell death
Summary
Renal cancer is a large heterogeneous group of cancers derived from renal tubular cells, and, as the seventh most common malignancy worldwide, the incidence is still increasing [1]. Clinical treatment often combines it with the adjacent affected kidney and resection [6, 7], so this study combined ACC with other renal cancer subtypes for analysis. Gene signatures associated with ferroptosis have been highly correlated with the clinical and pathological features of gliomas. They can serve as reliable indicators for the prognostic evaluation of glioma patients [13]. Ferroptosis-related genes such as GPX4 [14], NFE2L2 [15], and NOX1 [16] have been found to play a crucial role in tumorigenesis and progression, and these molecules are potentially essential players for cancer treatment and prognosis evaluation. A pan-renal cancer analysis was combined to evaluate the prognostic significance of each gene signature in different renal cancer subtypes
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