Systematic analysis of functional implications of fibrosis in pan-cancer

The common pathogenic mechanisms and molecular pathways of fibrosis and tumors remain unclear. We aimed to conduct in-depth analysis of fibrosis feature genes role from a pan-cancer perspective and identify potential therapeutic targets for idiopathic pulmonary fibrosis and cancers. We downloaded mRNA expression, copy number alterations, and DNA methylation data of 33 cancers from The Cancer Genome Atlas (TCGA). Clinical and mutation data were obtained from the UCSC Xena database. The mutation frequencies of fibrosis-feature-related genes (FRGs) in the TCGA database were examined. Protein expression levels were analysed using the Clinical Proteomics Tumor Analysis Consortium. Gene Set Variation Analysis and Gene Set Enrichment Analysis algorithms were used. Most FRGs were differentially expressed in tumors owing to somatic cell copy number alterations and DNA methylation. We established a fibrosis potential index (FPI), and in most cancers, the FPI was lower than that in normal tissues and correlated with subtypes and clinical features. The FPI correlated negatively with multiple metabolic pathways and immune function but positively with several important tumor features or pathways. The FPI correlated with prognosis in different tumors, despite finding heterogeneity. Fibrotic features have excellent diagnostic and prognostic capabilities for various cancers. This may help predict responses to immunotherapy.