Pan-Cancer Profiling and Digital Pathology Analysis Reveal Negative Prognostic Biomarker ZPR1 Associated with Immune Infiltration and Treatment Response in Hepatocellular Carcinoma

PURPOSE: ZPR1 is a zinc finger-containing protein that plays a crucial role in neurodegenerative diseases, lipid metabolism disorders, and non-alcoholic fatty liver disease. However, the expression pattern, prognostic value, and treatment response of ZPR1 in pan-cancer and hepatocellular carcinoma (HCC) remain unclear. PATIENTS AND METHODS: Pan-cancer expression profiles and relevant clinical data were acquired from UCSC Xena platform. Pan-cancer expression, epigenetic profile, and clinical correlation analysis for ZPR1 were performed. We next explored the prognostic significance and potential biological functions of ZPR1 in HCC. Furthermore, the relationship between ZPR1 and immune infiltration and treatment response was investigated. Finally, quantitative immunohistochemistry (IHC) analysis was applied to assess the correlation of ZPR1 expression and immune microenvironment in HCC tissues using Qupath software. RESULTS: ZPR1 was differentially expressed in most tumor types and significantly up-regulated in HCC. ZPR1 showed hypo-methylated status in most tumors. Pan-cancer correlation analysis indicated that ZPR1 was closely associated with clinicopathological factors and TMB, MSI, and stemness index in HCC. High ZPR1 expression could be an independent risk factor for adverse prognosis in HCC. ZPR1 correlated with immune cell infiltration and therapeutic response. Finally, IHC results suggested that ZPR1 correlated with CD4, CD56, CD68, and PD-L1 expression and is a promising pathological diagnostic marker in HCC. CONCLUSION: Immune infiltrate-associated ZPR1 could be considered a novel negative prognostic biomarker for therapeutic response in HCC.