Integrative Analysis of HMMR as a Potential Target of Prognosis and Therapy in Hepatocellular Carcinoma

Abstract

Background: Previous work has indicated Hyaluronic acid-mediated motor receptor (HMMR) plays an important role in regulating tumor metastasis. However, few researchers address the clinical significance of HMMR and its underlying mechanisms for regulating hepatocellular carcinoma (HCC). This study focuses on the underlying effect of HMMR in the development and prognosis of HCC. Materials and Methods: In the present study, data of RNA and miRNA sequencing array were obtained from Oncomine dataset or The Cancer Genome Atlas (TCGA) dataset, the distinctive genomic patterns associated with HMMR expression and its correlation with prognosis were analysed by using R package. Gene set enrichment analysis (GSEA) were performed on genes expressed aberrantly. We also performed Reverse Transcription-polymerase Chain Reaction (RT-PCR), Immunohistochemical (IHC) staining and Western blotting analysis to evaluate the expression of HMMR in liver cancer cell lines or 12 HCC samples from The Affiliated Hospital of Southwest Medical University. Results: A total of 407 tumor tissue samples in TCGA dataset were evaluated, combined with analysis in Oncomine dataset, we found HMMR expression was increased in HCC compared to normal tissues. Higher expression of HMMR was correlated with poorer overall survival and disease-free survival outcomes. Moreover, multivariate Cox regression analysis revealed that HMMR expression was an independent risk factor for overall survival (HMMR: hazard ratio [HR] = 1.154, 95% confidence interval [CI] = 1.080-1.233, p<0.001). Consistently, RT-PCR, IHC staining and Western blotting analysis further confirmed that HMMR expression was increased in HCC compared with patient-matched adjacent normal liver tissues. Notably, GSEA analysis revealed that differential gene expression in HMMR-high patients (compared with HMMRlow patients) were enriched in cell proliferation and p53 signaling pathway. Moreover, comprehensive analysis showed a strong correlation between HMMR upregulation and miRNA changes. Conclusion: The high expression of HMMR is a poor prognostic factor in HCC and might serve as a potential target of therapy in patients with HCC.