Classification of Colorectal Carcinoma Based on Ferroptosis-related Gene Signature

Abstract Background: Ferroptosis is an iron-dependent form of programmed cell death, involves in the development of many cancers. However, systematic analysis of ferroptosis related-genes in colorectal carcinoma (CRC) remains to be clarified. We herein analyzed the public databases to identify the molecular features of CRC by the development of a classification based on the gene expression profile of ferroptosis-related genes.Methods: We collected the gene expression data and clinical information from The Cancer Atlas and Gene Expression Omnibus to explore the correlation of ferroptosis-related gene expression of CRC. Consensus clustering was performed to determine the clusters of colorectal cancer patients, then we analyzed the prognostic value, transcriptome features, immune microenvironment, drug sensitivity, gene mutations differences of the subclasses. Results: Four subclasses of CRC (C1, C2, C3 and C4) were identified. There were significant differences in the prognosis of patients between the four subtypes. Functional enrichment suggested that these ferroptosis related-genes were associated with biological processes such as metabolic processes and oxidative stress, and the KEGG pathway suggested that it was closely related to ferroptosis and glutathione metabolic pathway. There were significant differences in immune cell infiltrations, immune score, stromal score and tumor purity among four subclasses. The expression of PD-L1 was differentially expressed in four subclasses and PD-L1 was significantly correlated with the expression of several ferroptosis-related genes in the differentially expressed subtypes. There were significant differences in stemness indices and drug sensitivity in four subclasses, and gene mutations analysis showed that ferroptosis-related genes such as TP53 had high mutations in different subtypes, and there were significant differences in mutation frequencies in the subclasses.Conclusion: This study established a new CRC classification based on ferroptosis-related genes expression profiles, and different subgroups may have their unique gene expression patterns, indicating that the heterogeneity within CRC and the classification might provide valuable stratification for the design of future treatment.