TIMM9 as a prognostic biomarker in multiple cancers and its associated biological processes.

ABSTRACT

TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.