Pan-cancer analysis unveiling the diagnostic, prognostic, and immunological role of crotonylation in human cancers

Abstract

Abstract Background Crotonylation is an important acylation modification, which regulates multiple physiological processes, such as RNA processing, nucleotide metabolism, chromatin reorganization, protein activity regulation, and protein localization. However, the managing mechanisms of crotonylation in cancer remain unknown. In the present study, a systematic pan-cancer analysis was performed to explore its diagnostic, prognostic, and immunological value across cancers. Method We consulted various public databases including Firehose database, UCSC Xena database, The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project, TIMER2.0, and TISCH databases for the extraction of pan-cancer data on crotonylation. We identified the mutation frequency, compared the mutation types, and depicted mutation profiles of crotonylation-associated genes. By the methods of GSVA and GSEA, we deeply excavated the biological role of crotonylation in pan-cancer, and clarified the association between crotonylation and drug resistance. Result Based on the TCGA data, we found that most of the crotonylation-related genes were differentially expressed in tumors, which was caused by somatic copy number alterations (SCNA) and DNA methylation. To reveal the functional role of crotonylation, we devised a novel term potential index (PI). PI was lower in tumor tissues than in normal tissues and had close correlations with different molecular subtypes and clinical features in most cancers. Moreover, PI was negatively correlated with multiple metabolic pathways and immune function, but positively associated with some important malignancy features or pathways. These findings contributed to gaining insight into the underlying mechanisms of tumor development and provided new ideas and approaches for anti-tumor therapy. Conclusion We found that crotonylation has excellent abilities to diagnose and predict prognosis in a variety of cancers. Furthermore, crotonylation may reshape the tumor microenvironment and induce an “immune desert” status, and therefore the potential of crotonylation-based cancer therapies has been underscored which simultaneously helps facilitate the capacity to predict the response to immunotherapy. As a result, crotonylation is expected to be an important target for future cancer treatments.