Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk

// Ying-Ying Jing 1, * , Wen-Ting Liu 1, * , Shi-Wei Guo 1, * , Fei Ye 1 , Qing-Min Fan 1 , Guo-Feng Yu 1 , Dan-Dan Yu 1 , Lu Gao 1 , Kai Sun 1, 2 , Zhi-Peng Han 1 , Rong Li 1 , Yang Yang 1 , Qiu-Dong Zhao 1 , Meng-Chao Wu 1 , Hong-Yang Wang 3 , Li-Xin Wei 1 1 Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China 2 Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 3 International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Li-Xin Wei, e-mail: weilixin_smmu@163.com Keywords: hepatitis B virus receptor, inflammation, hepatic progenitor cells, recurrence Received: May 26, 2015      Accepted: October 08, 2015      Published: October 20, 2015 ABSTRACT Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues ( P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP ( r = 0.461, P < 0.001) or ASGPR ( r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity ( P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation ( P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk ( P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients.