Altered protein lipidation in cancer: A hidden link to sensory neuronal dysfunction

Protein lipidation/delipidation affects protein functions, interactions, and membrane trafficking. Dysregulation of this process might lead to tissue disorganization, abnormal proliferation, migration, and poor prognosis in cancer. While dysregulation of lipidation/delipidation in neurons has been associated with several neurodegenerative diseases, its potential link to neuronal dysfunction in cancer patients remains unexplored. The aim of the study is to explore the association of altered protein lipidation with neurological problems in cancer patients via bioinformatic analysis. Gene list related to protein lipidation was retrieved and the effect of gene set alteration on overall survival on cancer patients was inquired using public dataset of cancer. Differentially expressed genes were analyzed for susceptibility to protein lipidation, distribution on chromosomes, Gene Ontology, and pathway enrichment analysis. Further enrichment and transcription factor targets analyses were performed. Differentially expressed genes (DEGs) in cancer patients with altered protein lipidation/delipidation were found to be associated with enrichment of neuronal regeneration/degeneration pathways, olfactory receptor signaling, and sensory perception pathways. Specifically, targets of Translational elongation factor EF-1 (TEF1) and signal transducer and activator of transcription 1 (STAT1) were enriched in the DEGs of patients with altered protein lipidation. Both TEF1 and STAT1 require lipidation for proper functioning. Therefore, altered lipidation in cancer patients could be associated with the disturbance of their downstream targets. These targets are significantly correlated to multiple pathways and processes related to neurological, sensory, and motor functions.