液泡蛋白分选相关蛋白29（VPS29）在癌症中发挥一定作用，但其在肝细胞癌（HCC）中的生物学意义尚未研究。我们利用生物信息学和孟德尔随机化（MR）分析来探讨VPS29基因在HCC中的潜在功能，以及VPS29蛋白与HCC之间的因果关系。我们从TCGA、GEO和IEU OpenGWAS数据库下载原始数据。我们使用R软件进行数据处理和分析，探讨VPS29基因与HCC患者的表达、预后、临床特征、甲基化、免疫微环境、肿瘤突变负荷和药物敏感性之间的关系。此外，还进行了两样本孟德尔随机分析，以探讨VPS29蛋白与HCC之间的因果关系。VPS29被发现在包括HCC在内的多种类型的癌症中过度表达，其表达升高往往预示着HCC患者预后不良。单变量和多变量 Cox 分析表明 VPS29 是 HCC 患者的独立预后因素。 ROC曲线表明VPS29对HCC具有较高的诊断价值。 VPS29在不同临床特征亚组中存在差异表达。 VPS29的表达与甲基化水平呈负相关，在启动子区域发现了多个甲基化位点，包括cg20877181、cg03867797、cg10025392、cg21605021，这些位点与低甲基化水平下较差的总生存(OS)相关。 VPS29与免疫细胞浸润紊乱相关，包括CD8 T细胞、嗜酸性粒细胞、中性粒细胞、Tcm、NK CD56bright细胞、TFH、Th2细胞、Th17细胞等。药物敏感性分析显示，VPS29可以指示10种常见抗肿瘤药物的治疗反应不同表达亚组的药物。逆方差加权 (IVW) 分析显示，与 VPS29 相关的 HCC 风险显着增加 [比值比 (OR)：1.440； 95%置信区间(CI)：1.195-1.736]，敏感性分析未显示异质性或多效性。VPS29是HCC发生和进展的危险因素，可作为HCC诊断和预后的分子生物标志物。

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.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.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.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.