Background: Hepatocellular carcinoma (HCC) is an inflammation-related malignancy influenced by the immune microenvironment, such as immune tolerance and evasion. HFUN14 domain-with protein 1 (FUNDC1) is a necessary mitochondrial outer membrane protein, functioning as a receptor for hypoxia-caused mitophagy, which is related to human immunity. The relationship between HCC and FUNDC1 in terms of prognosis and immunology was demonstrated in the current investigation. Even so, the function of FUNDC1 in liver cancer is yet unknown.
Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized for examining if FUNDC1 expression is associated with clinicopathological characteristics and prognosis. Genetic changes (mutation), DNA methylation, and their relationship with patient prognosis were identified by cBioPortal and MethSurv. Utilizing the Tumor Immune Estimation Resource (TIMER), immune checkpoints, infiltration, and immune cell biomarkers were analyzed. Utilizing the STRING database, the network of protein-protein interactions was created. Using Gene Set Enrichment Analysis, the FUNDC1 biological roles were determined (GSEA).
Results: FUNDC1 elevation was significantly linked with gender (p < 0.001), tumor stage (p = 0.01349), tumor grade (p < 0.001), and alpha-fetoprotein (AFP) (p < 0.001) levels in HCC. It was illustrated by ROC curve analysis that FUNDC1 had a significant diagnostic and prognostic value. The FUNDC1 genetic change rate was 0.6%. Four out of 6 DNA methylation CpG sites were associated with the HCC prognosis. FUNDC1 is associated strongly with immune cell infiltration in HCC. Moreover, FUNDC1 was positively related to immune checkpoints such as mutant-allele tumor heterogeneity (MATH) (p < 0.001), ploidy (p < 0.05), homologous recombination defect (HRD) (p < 0.001), and loss of heterozygosity (LOH). GSEA revealed significant FUNDC1 enrichment in the cell cycle, hedgehog, and MAPK signaling pathways.
Conclusion: FUNDC1 is a mitophagy regulator that could be a therapeutic, prognostic, and putative diagnostic biomarker for HCC.
Copyright © 2022 Yuyin Le et al.