Bin  Yu,Qinhui  Liu,Xuping Yang,Xin  Liu,Wanlong  Zhu,Xiaoyan  Zhong,Hengli  Luo,Qimin  Wei,Qingze  Fan,Yilan Huang,
Integrative Analysis of HMMR as a Potential Target of Prognosis and Therapy in Hepatocellular Carcinoma
Clinical Oncology and Research
2021
2613-4942
http://dx.doi.org/10.31487/j.COR.2021.01.01
https://www.sciencerepository.org/integrative-analysis-of-hmmr-as-a-potential-target-of-prognosis_COR-2021-1-101 
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.
Keywords:  Hepatocellular carcinoma, prognosis, HMMR, TCGA, therapeutic target