Reduced HBV cccDNA and HBsAg in HBV-associated hepatocellular carcinoma tissues

Tantiwetrueangdet, Anchalee; Panvichian, Ravat; Sornmayura, Pattana; Sueangoen, Natthaporn; Leelaudomlipi, Surasak

doi:10.1007/s12032-018-1191-7

Cited by 14 publications

(12 citation statements)

References 20 publications

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“…It is consistent with reports that there are lower viral loads in HBV infection HCC patients than in chronic HBV infection patients with cirrhosis . And, Tantiwetrueangdet et al reported that HBV cccDNA and intrahepatic HBsAg in HBV‐associated HCC tissues were significantly reduced, as compared with matched noncancerous tissues.…”

Section: Discussionsupporting

confidence: 87%

HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

Jiao

Shen

Ning

et al. 2019

Journal of Viral Hepatitis

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Summary It was repeatedly reported that the hepatitis B virus (HBV) T1719G mutation was very common and related to progression and malignancy of liver disease. However, its effect on viral replication efficiency remains unclear. In this study, we aimed to evaluate the function and mechanisms of the T1719G mutation on viral replication capacity. Wild‐type and T1719G mutation‐bearing HBV1.2× plasmids were transfected into Huh7 and HepG2 cells, respectively, and HBV total RNA, 3.5 kb RNA and supernatant HBV DNA were assessed using real‐time PCR, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured by time‐resolved fluoroimmunoassay. In order to assess Enh II activity and the binding capacity of HNF3β to Enh II sequence, dual‐luciferase assay and Chromatin immunoprecipitation (ChIP)‐PCR were employed, respectively. Simultaneously, the HBx or HBx‐mut (T1719G) plasmid was co‐transfected to evaluate the effect of HBx on viral replication. Our results showed that the T1719G mutation impaired viral replication efficacy compared with the wild type both by reducing Enh II activity and binding capacity of HNF3β with Enh II. And such reduction caused by T1719G mutation could be rescued by HBx protein. Our results show that the T1719G mutation decreases HBV viral replication capacity possibly by mutant HBx protein and altered Enh II activity.

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Section: Discussionsupporting

confidence: 87%

HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

Jiao

Shen

Ning

et al. 2019

Journal of Viral Hepatitis

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“…Three previous papers also reported the significantly reduced expression of HBsAg in HBV-associated HCC tissues compared with matched non-tumor tissues, and one paper attributed it to HBV integration in tumor cells. 29–31 However, no viral integrants were found in the tumor specimen from a patient in our study. According to the results from one of these papers that HBV receptors were deficient in tumor but over-expressed in peritumor, 30 HBV integrants in tumor tissues should be probably fewer than those in non-tumor tissues.…”

Section: Discussioncontrasting

confidence: 58%

Clinical, Pathological and Genetic Characteristics of Pediatric Hepatocellular Carcinoma Associated with Hepatitis B Virus Infection

Zhao¹,

Lu²,

Wang³

et al. 2021

JHC

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Introduction: Hepatocellular carcinoma (HCC) remains the major challenge in the management of patients with hepatitis B virus (HBV) infection. To date, limited studies have been done on pediatric HBV-associated HCC specifically. Methods: Pediatric patients younger than 16 years with HBV-associated HCC were included in the study. HBV integration detection was performed using a high-throughput viral integration detection (HIVID) method. Results: Among the 13 included pediatric patients, boys predominated (10, 76.9%). The median age at diagnosis of HCC was 13 years and the youngest age was 6 years. Nine patients had initially seronegative hepatitis B e antigen (HBeAg) and 4 had seropositive HBeAg. All patients had cirrhosis and elevated alpha-fetoprotein. Splenomegaly was present in all patients. Intrahepatic HBsAg was not detected in any tumor tissues from 5 patients who underwent biopsy or excision, while it was positive in all matched non-tumor tissues. In the tumor and matched non-tumor tissues from 3 individuals, HBV integration was identified except in the neoplastic specimen from 1 patient. Integration into the reported genes associated with hepatocarcinogenesis was not found in the tumor tissues from the 3 patients. Discussion: Hypervigilance for HCC development is required in HBeAg-negative cirrhotic children. The findings based on the immunohistochemical and genetic results expand the knowledge of pediatric HCC development.

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“…The cut-off value for p53 protein positivity was a p53 staining with positive nuclei in ≥1% of cells, regardless of the staining intensity, as we previously reported [ 24 ]. The cut-off value for HBsAg protein positivity was an HBsAg staining with positive cytoplasmic staining > 1 cell in each tissue section, as we previously reported [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues

et al. 2021

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Background PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC. Methods KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR (qRT-PCR) in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues. KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation. The relationships between KIAA0101 protein expression and other clinicopathological parameters, including Ki-67, p53, and HBsAg protein expression in HCC tissues, were evaluated using Chi-square test. Results Our results demonstrated that KIAA0101/PCLAF mRNA levels were significantly higher in HCC than in the matched-non-cancerous tissues (p < 0.0001). The high KIAA0101/PCLAF mRNA levels in HCC were associated with poor patient survival. The KIAA0101/PCLAF gene was not amplified in HCC, and KIAA0101/PCLAF gene copy numbers were not associated with KIAA0101/PCLAF transcript levels. KIAA0101 protein was overexpressed in the majority of HCC tissues (77.8%) but was not detectable in matched-non-cancerous tissues. Significant correlations between the expression of KIAA0101 protein in HCC tissues and p53 tumor suppressor protein (p = 0.002) and Ki-67 proliferation marker protein (p = 0.017) were found. However, KIAA0101 protein levels in HCC tissues were not correlated with patient age, tumor size, serum AFP level, or the HBsAg expression. Conclusions KIAA0101/PCLAF mRNA and protein overexpression is frequently observed in HCC but without concurrent KIAA0101/PCLAF gene amplification. Significant correlations between the expression of KIAA0101 protein and p53 and Ki-67 proteins were observed in this study. Thus, detection of KIAA0101/PCLAF mRNA/protein might be used, along with the detection of p53 and Ki-67 proteins, as potential biomarkers to select candidate patients for further studies of novel HCC treatment related to these targets.

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Reduced HBV cccDNA and HBsAg in HBV-associated hepatocellular carcinoma tissues

Cited by 14 publications

References 20 publications

HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

Clinical, Pathological and Genetic Characteristics of Pediatric Hepatocellular Carcinoma Associated with Hepatitis B Virus Infection

PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues

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