Dataset Information

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.

ABSTRACT: BACKGROUND:Epstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2IVS2-848C-->T, PIGRIVS3-156G-->T, PIGR1093G-->A and PIGR1739C-->T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins. RESULTS:The results obtained indicated that PIGR is an NPC susceptibility gene. The risk association pertaining to each ethnic group was detected for homozygous PIGR1739C with a significant ethnic group adjusted OR (95%CI) of 2.71(1.72-4.23) and p < 0.00001. Haplotype of the two missense PIGR SNPs, 1093G-->A and 1739C-->T, and sequence analyses have confirmed the role of the nucleotide PIGR1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP. CONCLUSIONS:We present genetic evidence leading to hypothesize a possibility of PIGR to function as the EBV nasopharyngeal epithelium receptor via IgA-EBV complex transcytosis failure. The PIGR1739C-->T is a missense mutation changing alanine to valine near endoproteolytic cleavage site. This variant could alter the efficiency of PIGR to release IgA-EBV complex and consequently increase the susceptibility of populations in endemic areas to develop NPC.

SUBMITTER: Hirunsatit R

PROVIDER: S-EPMC149362 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.

Hirunsatit Rungnapa R Kongruttanachok Narisorn N Shotelersuk Kanjana K Supiyaphun Pakpoom P Voravud Narin N Sakuntabhai Anavaj A Mutirangura Apiwat A

BMC genetics 20030121

<h4>Background</h4>Epstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2IVS2-848C--> ...[more]

PMID: 12546713

Similar Datasets

Project description:BACKGROUND:High expression of the polymeric immunoglobulin receptor (PIGR) has previously been associated with a favourable prognosis in a few cancer forms, but its expression and relationship with clinical outcome in epithelial ovarian cancer (EOC) has not yet been reported. The aim of this study was therefore to examine the clinicopathological correlates and prognostic significance of PIGR expression in EOC. METHODS:After an initial screening in the Human Protein Atlas portal, a validated antibody was selected for extended analysis of immunohistochemical PIGR expression in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian tubes (n?=?38) and omental metastases (n?=?33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were applied to examine the impact of PIGR expression on overall survival (OS) and ovarian cancer-specific survival (OCSS). RESULTS:PIGR expression was significantly higher in fallopian tubes compared to primary tumours and metastases (p?<?0.001) and lower in carcinoma of the serous subtype compared to other carcinomas (p?<?0.001). PIGR expression was significantly associated with lower grade (p?=?0.001), mucinous histological subtype (p?=?0.002), positive progesterone receptor expression (p?=?0.009) and negative or low Ki-67 expression (p?=?0.003). Kaplan-Meier analysis revealed a significantly improved OS (p?=?0.013) and OCSS (p?=?0.009) for patients with tumours displaying high expression of PIGR. These associations were confirmed in unadjusted Cox regression analysis (HR?=?0.48; 95% CI 0.26-0.87; p?=?0.015 for OS and HR?=?0.43, 95% CI 0.22-0.82; p?=?0.011 for OCSS) but did not remain significant after adjustment for age, grade and clinical stage. CONCLUSIONS:This study provides a first demonstration of PIGR expression in human fallopian tubes, primary EOC tumours and metastases. High tumour-specific expression of PIGR was found to be associated with a favourable prognosis in unadjusted, but not in adjusted, analysis. These findings are novel and merit further investigation.

Project description:Background & Aims: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells and their local and distant microenvironment. Here, we aimed to understand the role and molecular basis of patient-derived EVs in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). Methods: EVs were isolated, quantified and characterized from patients’ sera. EVs were tested vigorously, both in vitro and in vivo, by various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The expression level of polymeric immunoglobulin receptor (pIgR) in circulating EVs, tumor and non-tumorous tissues of HCC patients was determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with an enhanced pIgR expression was elucidated. Blockage of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenograft (PDTX). Results: Circulating EVs of late-stage HCC (L-HCC) patient had significantly elevated pIgR expression when compared to the EVs released by control individuals. The augmenting effect of L-HCC patient in cancer stemness and tumorigenesis was hindered by anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in the recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and β-catenin inhibitors, ascertaining the role of EV-pIgR through the activation of PDK1/Akt/GSK3β/β-catenin signaling axis. Furthermore, anti-pIgR neutralizing antibody attenuated the tumor growth in mice implanted with PDTX. Conclusion: The study illustrates an unrevealed role of EV-pIgR in regulating cancer stemness and aggressiveness, in which EV-pIgR activates PDK1/Akt/GSK3β/β-catenin signaling cascades. The blockage of intercellular communications mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for cancer patients.

Dataset Information

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.

Publications

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets