High level of HDGF expression in hepatocellular carcinoma: a potential therapeutic target associated with prognosis and immune infiltration

Abstract

Abstract Background Evaluations of hepatoma-derived growth factor (HDGF) expression may possess prognostic value for several cancers, including hepatocellular carcinoma (HCC). However, its functions and underlying mechanisms in HCC remain to be elucidated. The current study was designed to investigate the expression patterns of this protein, its prognostic value, immune characteristics and potential molecular mechanisms of HDGF in HCC. Methods Clinical and gene expression data were collected. The Kaplan–Meier method, time-dependent receiver operating characteristic (ROC) curves, and Cox regression analysis were used to analyze the prognostic value of HDGF. Differences in HDGF expression were analyzed using DESeq2 in R and gene ontology, KEGG, and GSEA were used to determine the biological functions of HDGF. Both the estimate and SsGSEA methods were used to analyze the immune infiltrates of HCC. Illumina human methylation 450 data and level 3 HTSeq-FPKM data from TCGA-LIHC cohort were used to determine the effects of DNA methylation on HDGF expression. Results HDGF was overexpressed in HCC and its expression correlated with T stage, pathological stage, histological grade, and AFP levels. Furthermore, we revealed the HDGF acts as an independent risk factor for overall survival in HCC and its expression is associated with the tumor-immune microenvironment and immune infiltration, especially in terms of cytotoxic, pDC and Th2 cell populations. Our data also suggests increased HDGF expression in HCC is associated with demethylation of its promoter region. Conclusions HDGF independently predicts unfavorable prognosis and regulates the immune microenvironment of HCC, identifying HDGF as a potential immunotherapeutic target for HCC.