β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development.

Yue-Ming Ling ; Jin-Yu Chen ; Libin Guo ; Chen-Yi Wang ; Wen-Ting Tan ; Qing Wen ORCID logo ; Shu-Dong Zhang ORCID logo ; Guo-Hong Deng ; Yao Lin ORCID logo ; Hang Fai Kwok ; (2017) β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development. Scientific reports, 7 (1). 13404-. ISSN 2045-2322 DOI: 10.1038/s41598-017-13332-0
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β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development.


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