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

• Published in: Scientific reports Vol. 14; no. 1; pp. 20568 - 21
• Main Authors: Zhang, Lisheng, Huang, Yan, Yang, Yanting, Liao, Birong, Hou, Congyan, Wang, Yiqi, Qin, Huaiyu, Zeng, Huixiang, He, Yanli, Gu, Jiangyong, Zhang, Ren
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-09-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/67; Adaptive immunity; Bioinformatics; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cell cycle; Colorectal cancer; Computational Biology - methods; Copy number; DNA Copy Number Variations; Drug resistance; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Investigations; Liver cancer; Lung cancer; Medical prognosis; Metabolism; Metabolism reprogramming; Metastases; Metastasis; Methylation; Missense mutation; Mitochondria; Mitochondrial Precursor Protein Import Complex Proteins - metabolism; multidisciplinary; Mutation; Mutation, Missense; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Ovarian cancer; Oxidative phosphorylation; Pan-cancer; Phosphorylation; Prognosis; Proteins; Science; Science (multidisciplinary); Signal Transduction; TOR protein; Tricarboxylic acid cycle; Tumorigenesis; Tumors; Mitochondria; Metabolism reprogramming; Oxidative phosphorylation; Drug resistance; Pan-cancer
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71421-3

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.