Background: Hepatocellular carcinoma (HCC) is a malignant tumor with complex pathogenesis. In HCC, the possible roles of transcriptional factor WD repeat and HMG-box DNA binding protein 1 (WDHD1) remain unclear. Hence, our study is aimed at verifying the prognosis prediction ability and potential biological mechanisms of WDHD1 in HCC.

Results: In this study, a total of 7171 clinical samples were obtained to quantitatively analyze the protein and mRNA expression levels of WDHD1 by using immunohistochemistry, gene microarrays, and high-throughput sequencing technologies. The result of in-house immunohistochemistry assay indicated that WDHD1 protein was remarkably overexpressed in HCC tissues compared with the non-HCC tissues (AUC > 0.99, the single Standardized Mean Difference [SMD] = 4.46). The overexpression trend of WDHD1 was validated by the comprehensive analysis based on a total of 4004 HCC tissues and 3167 controls (SMD = 1.333; AUC = 0.91). Moreover, the higher WDHD1 expression resulted in the poorer prognosis of HCC, as assessed by overall survival and relapse-free survival analyses (pooled hazard ratios > 1). WDHD1-coexpressed genes were screened out for enrichment analyses to enquire the prospective signaling pathways of WDHD1 in HCC and to probe the potential transcriptional targets of WDHD1. The WDHD1-coexpressed genes were mainly involved in the division process of chromosome and cell nucleus in HCC. UBA52 was identified as a crucial target of WDHD1.

Conclusions: WDHD1 may act as an oncogene in HCC and it has the potential to become a novel marker for predicting the prognosis of HCC patients, which may benefit from the early intervention of HCC.