PTPN3 Mutations and HBV May Exert Synergistic Effects in the Origin of the Intrahepatic Cholangiocarcinoma

Cardinale, Vincenzo; Alvaro, Domenico

doi:10.1053/j.gastro.2014.05.046

Cited by 5 publications

(5 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,14 Cardinale et al suggested that the interactions between PTPN3 mutations and HBV proteins may lead to intrahepatic cholangiocarcinoma. 31 Another likely explanation is that chronic HBV infection may lead to development of cirrhosis, which is a risk factor for intrahepatic cholangiocarcinoma. 18 Notably, we also found a borderline significant association between HBV infection and cancers of the Ampulla of Vater and extrahepatic bile ducts.…”

Section: Discussionmentioning

confidence: 53%

See 1 more Smart Citation

Hepatitis B virus infection and the risk of cancer in the elderly US population

Mahale

Engels

Koshiol

2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma (HCC). Associations with other cancers are not established. We systematically assessed associations between HBV infection and cancers in the US elderly population. We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database in US adults aged ≥66 years. Cases (N = 1,825,316) were people with first cancers diagnosed in SEER registries (1993-2013). Controls (N = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race and calendar year. Associations with HBV infection (ascertained by Medicare claims) were assessed by logistic regression. HBV prevalence was higher in cases than controls (0.6% vs. 0.5%). HBV was positively associated with cancers of the stomach (adjusted odds ratio [aOR] = 1.19; 95% confidence intervals [CI] = 1.03-1.37), anus (1.66; 1.17-2.33), liver (10.6; 9.66-11.6), intrahepatic bile ducts (1.67; 1.18-2.37), nasopharynx (2.08; 1.33-3.25), as well as myelodysplastic syndrome (1.26; 1.07-1.49) and diffuse large B-cell lymphoma (DLBCL) (1.24; 1.06-1.46). Inverse associations were observed with female breast (aOR = 0.86; 95%CI = 0.76-0.98) and prostate (0.81; 0.73-0.91) cancers and chronic lymphocytic leukemia (0.77; 0.62-0.96). Associations were maintained in sensitivity analyses conducted in people without claims for cirrhosis or hepatitis C or human immunodeficiency virus infections. HBV infection is associated with increased risk of cancers other than HCC, such as bile duct cancers and DLBCL. The biological mechanisms by which HBV may lead to these cancers need to be explored.

show abstract

Section: Discussionmentioning

confidence: 53%

“…Cardinale et al . suggested that the interactions between PTPN3 mutations and HBV proteins may lead to intrahepatic cholangiocarcinoma . Another likely explanation is that chronic HBV infection may lead to development of cirrhosis, which is a risk factor for intrahepatic cholangiocarcinoma .…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus infection and the risk of cancer in the elderly US population

Mahale

Engels

Koshiol

2018

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The NMR binding experiments between PTPN3-PDZ and full-length HBc as CLPs were performed at 20 °C on a 600-MHz BRUKER Avance III HD spectrometer equipped with a cryoprobe. Briefly, the unlabeled HBc (stock solutions at 7.1 mM) were added in a sample initially containing 270 μL of 15…”

Section: Analytic Ultracentrifugation (Auc) Experiments Hbcmentioning

confidence: 99%

“…Thus, we propose that targeting PTPN3 through a PBM-PDZ interaction may be significant to the viral life cycle and/or in the oncogenic character of HBV. Notably, PTPN3 has been implicated in many cancers [9][10][11][12][13][14] , and it has been suggested that PTPN3 mutations and HBV may exert synergistic effects in the origin of the intrahepatic cholangiocarcinoma 15 . We further investigated the role of PTPN3 in a cell model system of Human hepatoma HepG2 NTCP cells stably expressing full-length PTPN3 under HBV infection to explore and to document the presence of this PBM in HBV core protein.…”

mentioning

confidence: 99%

Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein

Genera

Quioc-Salomon

Nourisson

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.

show abstract

“…In lung cancer, PTPN3 has been shown to limit cellular proliferation and invasion by increasing EGFR endocytic degradation [ 10 , 11 ]. PTPN3 is favorably correlated with a better prognosis in perihilar cholangiocarcinoma and to slow down the growth of the malignancy by blocking AKT phosphorylation [ 12 , 13 ]. However, PTPN3 may have a dual role in the development of various malignancies.…”

Section: Introductionmentioning

confidence: 99%

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Zhou,

Lin,

Wang

et al. 2024

Eur J Med Res

View full text Add to dashboard Cite

Background The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. Methods The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. Results PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. Conclusions Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

show abstract

PTPN3 Mutations and HBV May Exert Synergistic Effects in the Origin of the Intrahepatic Cholangiocarcinoma

Cited by 5 publications

References 7 publications

Hepatitis B virus infection and the risk of cancer in the elderly US population

Hepatitis B virus infection and the risk of cancer in the elderly US population

Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy

Contact Info

Product

Resources

About