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.

Paraoxonase 3 inhibits cell proliferation and serves as a prognostic predictor in hepatocellular carcinoma

“…PON3 staining was enriched in the cytoplasm as previously reported [15], and PON3 staining was significantly reduced in HCC tissues (Figure 1D). Methodology to quantitate the staining level has been described [16]. In agreement with the qRT-PCR and Western-blot results, the protein level of PON3 was significantly lower in most HCC tissues (253 of 286 patients) in the tissue microarray cohort (Figure 1E).…”

“…Immunohistochemistry was performed as previously described [16]. A PON3 polyclonal antibody (Abcam, MA, USA) diluted at 1:300 was used as the primary antibody.…”

Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy

“…The assessment of necroinflammatory activity was based on the extent and distribution of the predominantly inflammatory infiltrate characteristics including portal, periportal, and intra-acinar inflammatory cell infiltration, and liver cell necrosis. Briefly, necroinflammatory activity in the liver tissues was divided into the following four levels: Grade 1 (1-4): no activity; Grade 2 (5-8): mild; Grade 3 (9-12): moderate; and Grade 4 (13)(14)(15)(16)(17)(18): severe [20,21].…”

Down-regulation of NTCP expression by cyclin D1 in hepatitis B virus-related hepatocellular carcinoma has clinical significance

“…Given the association between NTCP expression and cell proliferation status, it is reasonable to assume that the expression of NTCP might be suppressed in HCC tumor tissues. Indeed, recent works have identified the down-regulation of NTCP expression in HCC tumor tissues [ 13 , 15 ]. However, the relationship between NTCP down-regulation and the development of HBV-related HCC are not fully understood.…”