Potential functions and causal associations of VPS29 in hepatocellular carcinoma: a bioinformatic and Mendelian randomization study

Y.-Q. Yao, J.-L. Lv

Guangxi University of Chinese Medicine, Nanning, China. lvjl@gxtcmu.edu.cn

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• Genetics
• Oncology

OBJECTIVE: Vacuolar protein sorting-associated protein 29 (VPS29) plays a certain role in cancer, but its biological significance in hepatocellular carcinoma (HCC) has not been studied. We utilized bioinformatics and Mendelian randomization (MR) analysis to explore the potential function of the VPS29 gene in HCC, as well as the causal relationship between VPS29 protein and HCC.

MATERIALS AND METHODS: We downloaded the raw data from TCGA, GEO, and IEU OpenGWAS databases. We used R software for data processing and analysis to explore the relationship between the VPS29 gene and the expression, prognosis, clinical features, methylation, immune microenvironment, tumor mutation burden, and drug sensitivity in HCC patients. Additionally, a two-sample Mendelian randomization analysis was conducted to investigate the causal relationship between the VPS29 protein and HCC.

RESULTS: VPS29 was found to be overexpressed in various types of cancer, including HCC, and its elevated expression often predicts poor prognosis in HCC patients. Univariate and multivariate Cox analysis demonstrated that VPS29 was an independent prognostic factor in HCC patients. The ROC curve indicated that VPS29 has a high diagnostic value in HCC. There were differential expressions of VPS29 in various clinical feature subgroups. The expression of VPS29 was negatively correlated with methylation levels, and multiple methylation sites were identified in the promoter region, including cg20877181, cg03867797, cg10025392, cg21605021, which were associated with poorer overall survival (OS) at low methylation levels. VPS29 was associated with immune cell infiltration disorders, including CD8+ T cells, Eosinophils, Neutrophils, Tcm, NK CD56bright cells, TFH, Th2 cells, Th17 cells, etc. Drug sensitivity analysis showed that VPS29 could be indicative of treatment response to 10 common antineoplastic drugs in different expression subgroups. Inverse variance weighted (IVW) analysis revealed a significant increase in HCC risk associated with VPS29 [odds ratio (OR): 1.440; 95% confidence interval (CI): 1.195-1.736], and sensitivity analysis showed no heterogeneity or pleiotropy.

CONCLUSIONS: VPS29 is a risk factor for the occurrence and progression of HCC and may serve as a molecular biomarker for the diagnosis and prognosis of HCC.

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