Pan-cancer analysis unveils the role and mechanisms of neddylation modifications in tumorigenesis.

Abstract

This study explores the roles of ubiquitin-like modification genes in pan-cancer, focusing on their regulatory mechanisms, prognostic implications, and drug sensitivity. Data on five key neddylation pathway genes (RBX1, NEDD8, NAE1, UBA3, UBE2M) were collected from TCGA and GTEx databases, covering mRNA expression, DNA methylation, SNVs, and CNVs. Gene expression differences between normal and cancer tissues, along with associations with genetic alterations, methylation, and cancer-related pathways, were analyzed. Drug sensitivity correlations were assessed using GDSC and CTRP databases. Neddylation pathway genes exhibit hypomethylation and overexpression across various cancers, correlating with poor prognosis. SNVs are predominantly missense mutations, while CNVs are mostly heterozygous deletions and amplifications. These genes regulate several key cancer-related pathways, such as DNA damage repair, cell cycle modulation, and inhibition of RTK/RAS/MAPK pathways. Ubiquitin-like modification genes are associated with poor prognosis due to their low methylation and high expression in cancers. Their genetic alterations impact cancer pathways, underscoring their potential as therapeutic targets and prognostic biomarkers.