Prognostic Value of VPS45 in HCC and Its Correlation with Immune Microenvironment

Jiming Duan,1,* Wenjun Zhao,2,* Na Lv,2 Changhu Xie,2 Guoping Zhang,2 Lei Zhang,2,* Renhou Zhi2,*1Department of General Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, People’s Republic of China; 2Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renhou Zhi, Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China, Email zhirenhou@sxbqeh.com.cn Lei Zhang, Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China, Email zhanglei@sxbqeh.com.cnPurpose: A growing body of research indicates that Vacuolar Protein Sorting 45 (VPS45) is essential for the development of tumours and the advancement of cancer. Its biological role and expression profile in HCC are still mostly unknown, nevertheless.Materials and Methods: Using a variety of datasets, including the Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), among others, we examined the existence and prognostic importance of VPS45. Functional enrichment analysis was employed to elucidate the potential mechanisms through which VPS45 may influence HCC. Additionally, we assessed the relationship between VPS45 expression and immune cell infiltration using single-sample gene set enrichment analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumour tissues using Expression data (ESTIMATE). The Tumor Immune Dysfunction and Rejection (TIDE) algorithm was leveraged to assess the sensitivity of predicted gene expression to immunotherapy. Utilizing assays including CCK-8, wound healing, and Transwell migration and invasion methods, we performed in vitro experiments on the MHCC-97H cell line to further investigate the biological significance of VPS45 in the progression of hepatocellular carcinoma (HCC).Results: According to our research, VPS45 expression is markedly elevated in HCC, and elevated VPS45 levels are associated with a worse prognosis for patients. Functional enrichment analysis showed that elevated VPS45 expression is closely linked to the activation of various oncogenic pathways. VPS45 silencing decreases HCC cell invasion, metastasis, and proliferation, according to in vitro investigations. Interestingly, it was shown that VPS45 levels showed a positive link with immunosuppressive cell populations and related genes, but a negative correlation with a number of anti-tumor immune cell types. Immunotherapy resistance is more common in patients with increased VPS45 expression.Conclusion: This study clarifies the biological role of VPS45 in hepatocellular carcinoma (HCC) and, through comprehensive database analyses combined with in vitro experiments, supports its potential as a diagnostic and predictive biomarker for HCC. In addition to its value for disease detection and prognosis, VPS45 may help predict patient response to immunotherapy.Keywords: hepatocellular carcinoma, VPS45, prognosis, immune infiltration, immunotherapy