Pan-Cancer Analyses Confirmed the Ferroptosis-Related Gene SLC7A11 as a Prognostic Biomarker for Cancer

Abstract

Purpose: Ferroptosis is an iron-dependent and reactive oxygen species (ROS)-reliant form of cell death, exhibiting cellular, molecular, and gene-level characteristics distinct from those of necrosis, autophagy, apoptosis, and pyroptosis. Solute carrier family 7 member 11 (SLC7A11), which encodes a cystine/glutamate antiporter transmembrane protein, inhibits ferroptosis by importing cystine and promoting glutathione (GSH) biosynthesis and was found to be overexpressed in multiple human cancers. However, the specific role and underlying mechanism of SLC7A11 in cancers remains poorly characterized. This research aimed to identify the relationship between SLC7A11 expression and tumor microenvironment and visualize its prognostic value in pan-cancer. Patients and Methods: Transcriptomic data for 6313 tumors and normal samples across 20 cancer types were acquired from The Cancer Genome Atlas (TCGA) database. Besides, we presented a novel bioinformatics pipeline that uncovered the impacts of SLC7A11 on cancer prognosis, tumor mutational burden (TMB), immune cell infiltration in tumor microenvironment, and drug responses. The Genotype-Tissue Expression (GTEx), cBioportal, TCGA and Connectivity Map (CMap) databases were used to explore the expression, genetic alterations, immune microenvironment, and drug responses of SLC7A11. A series of deconvolution algorithms, including EPIC, CIBERSORT and GSEA, were utilized for multidimensional analyses of the cancer transcriptomic data. Results: SLC7A11 was found to be highly expressed in the 20 types of cancer, especially in solid tumors. Survival analysis uncovered that most cancer patients with up-regulated expression of SLC7A11 showed poor prognosis, suggesting that SLC7A11 is a potential oncogene in most cancer types. Furthermore, the expression level of SLC7A11 was confirmed to be associated with immune cell infiltration in tumor microenvironment, TMB, and drug responses. Gene set enrichment analysis (GESA) revealed that dysregulation of SLC7A11 was associated with metabolic and immunity-related signaling pathways in the cancers. Conclusion: The comprehensive pan-cancer analyses identified SLC7A11 as an attractive biomarker for immune infiltration and poor prognosis in cancers, shedding new light on the therapeutics of cancers.