Integrative analysis of h-prune as a potential therapeutic target for hepatocellular carcinoma

BACKGROUND: Drosophila prune protein (h-prune) has been proved to play an essential role in regulating tumor metastasis. However, the clinical relevance of h-prune and its potential mechanism in regulating hepatocellular carcinoma (HCC) are still poorly understood. METHODS: In this study, we used tissue microarrays (TMA) containing 304 HCC tumor samples to evaluate the expression of h-prune and its correlation with prognosis. Data of RNAseq, mutation profiles, copy number variation (CNV), miRNAseq and methylation array from The Cancer Genome Atlas (TCGA) dataset were adopted to analyze the distinctive genomic patterns associated with h-prune expression. RESULTS: By using TMA, we found increased expression of h-prune in HCC tumor cells compared with adjacent normal tissues. Higher expression of h-prune was correlated with poorer OS and DFS outcomes. In addition, multivariate analysis showed that h-prune expression was an independent risk factor for both OS and DFS. Gene enrichment analysis showed that the gene signatures of cell proliferation, DNA methylation and canonical Wnt signaling pathway were enriched in h-prune-high patients. Notably, somatic mutation analysis demonstrated that higher mutation burden of RB1 and RPS6KA3 could be observed in h-prune-high patients. Moreover, integrative analysis revealed a strong correlation between h-prune expression and epigenetic changes. INTERPRETATION: This study has highlighted the clinical value of h-prune in predicting the prognosis of HCC patients and its essential role in promoting tumorigenesis of HCC.