Clinical significance and functional analysis of NADH: ubiquinone oxidoreductase complex assembly factor 2 in liver cancer

Abstract

Abstract: Objective:To investigate the expression characteristics, clinical and prognostic significance as well as potential functional mechanisms of NADH: ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2) in liver cancer based on multi-omics data from The Cancer Genome Atlas (TCGA) database.
Method:RNA sequencing, whole exome sequencing, single nucleotide polymorphism microarray and DNA methylation sequencing data of TCGA liver cancer samples were used to analyze the expression characteristics and possible causes for abnormally high expression of NDUFAF2 in liver. The highly correlated co-expressed genes with NDUFAF2 were used to perform the pathways and human phenotype enrichment analyses, and then the functional network was constructed using Cytoscape software.
Result:Expression and survival analysis based on RNA sequencing data from liver cancer patients of TCGA showed that among all subunits of the mitochondrial respiratory complexes, only NDUFAF2 was significantly overexpressed in tumor tissues and correlated with unfavorable overall survival and recurrence-free survival. Elevated expression of NDUFAF2 was associated with gender, race, tumor differentiation and microvascular invasion (all P<0.05). Copy number gain, TP53 and CTNNB1 missense mutation as well as MYC amplification but not promoter methylation were all responsible for high NDUFAF2 expression in tumor. The enrichment analysis of 411 genes that co-expressed with NDUFAF2 revealed that NDUFAF2 may contribute to hepatocarcinogenesis by regulating cellular energy production, oxidative stress, RNA processing, protein translation and c-Myc and mTORC1-related pathways.
Conclusion:Elevated expression of NDUFAF2 in liver cancer maybe engage in carcinogenesis by facilitating RNA processing, protein translation and intracellular signaling pathways. NDUFAF2 can serve as a potential prognostic marker and a new target for therapeutic intervention for liver cancer.

Key words: NADH: ubiquinone oxidoreductase complex assembly factor 2, Liver cancer, Public database mining, Prognosis, Expression regulation, Tumorigenesis

Zhu Ying, Gu Xinglu, Zhao Xiaohang, Sun Yulin. Clinical significance and functional analysis of NADH: ubiquinone oxidoreductase complex assembly factor 2 in liver cancer[J]. Electronic Journal of Liver Tumor, 2022, 9(1): 29-35.

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