title: Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk.
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.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Jing
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Guo
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Qing-Min
authors.initials: QM
authors.lastname: Fan
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Yu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.|Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Han
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Qiu-Dong
authors.initials: QD
authors.lastname: Zhao
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037263:Asialoglycoprotein Receptor / Q000032:analysis / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D002648:Child; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation / Q000473:pathology / Q000821:virology; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000821:virology*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000032:analysis / Q000096:biosynthesis; D027981:Symporters / Q000032:analysis / Q000096:biosynthesis; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D037263:Asialoglycoprotein Receptor; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: hepatic progenitor cells; hepatitis B virus receptor; inflammation; recurrence