Abstract
Objective
This study aims to explore ADH4 in hepatocellular carcinoma (HCC), its prognosis impact, and immune correlation for novel insights into HCC prognostication and treatment.
Methods
HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The interested markers (DNASE1L3, RDH16, ADH4, LCAT, HGFAC) in HCC and adjacent tissues were assessed by Immunohistochemistry (IHC). ADH4 expression were validated by symbol rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4 related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues.
Results
ADH4 showed significant downregulation in various cancers, particularly in HCC. Immunohistochemistry analysis confirmed reduced ADH4 expression in HCC tissues compared to normal liver tissues. Moreover, ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Our nomograms based on ADH4 expression, tumor status, and T stage demonstrated its clinical prognostic significance. Additionally, ADH4 exhibited immunoregulatory functions in the HCC microenvironment, correlating with immune cell infiltration patterns. Furthermore, ADH4 expression inversely correlated with several immune checkpoint markers, suggesting its potential as a therapeutic target in HCC immunotherapy.
Conclusion
This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.