Search

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)‐associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost‐effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI‐W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI‐W 121 bp and ebv‐miR‐BART7‐3p were validated. Hsa‐miR‐29a‐3p and hsa‐miR‐103a‐3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI‐W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling. What's new? Plasma Epstein–Barr virus (EBV) DNA is an established nasopharyngeal carcinoma (NPC) biomarker, but not all cases are associated with EBV and its sensitivity for stage I NPC remains controversial. Meanwhile, most newly‐reported NPC biomarkers have neither been externally validated nor compared to established biomarkers. This study systematically evaluates six established and four new biomarkers in NPC cases, population controls, and hospital controls. The findings provide evidence to policymakers for improvement in NPC screening and monitoring strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity/specificity, and testing multiple biomarkers on single specimens to avoid the logistic problems of resampling. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway ( pGWAS-GSEA = 1.98 × 10−2; pExpr-GSEA = 1.27 × 10−24; pBonf-Combined = 4.15 × 10−21). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues ( pAmpliSeq-GSEA = 6.56 × 10−4). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 ( p = 1.73 × 10−9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove ( pHLA-A-aa-site-99 = 3.79 × 10−8, prs1136697 = 3.79 × 10−8) and T-cell receptor binding site ( pHLA-A-aa-site-145 = 1.41 × 10−4, prs1059520 = 1.41 × 10−4) of the HLA-A. We also detected strong association signals in the 5′-UTR region with predicted active promoter states ( prs41545520 = 7.91 × 10−8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese. [ABSTRACT FROM AUTHOR]

Objectives: This study examines the presence of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) by using polymerase chain reaction (PCR).Study Design: Eighty-six postnasal biopsy samples and 71 fine-needle aspirate samples of neck masses were obtained from patients who were clinically suspect for NPC. Genomic DNA was extracted from the samples, and EBNA1, EBNA2, and LMP genes of EBV were detected by PCR. PCR results were compared with NPC histopathology findings.Results: The sensitivity of PCR to detect EBNA1 (97.14%), EBNA2 (88.57%), and LMP (91.43%) genes of EBV in nasopharyngeal biopsy samples were higher than those in fine-needle aspirate samples.Conclusion: Detection of EBV by PCR in tissue obtained from nasopharyngeal biopsy and fine-needle aspirate samples of neck masses is a relatively inexpensive, reliable, and accurate method of diagnosing NPC. Detection of EBV genes is on par with histopathological examination (HPE) and superior to fine-needle aspirate cytology.Significance: PCR is an ideal tool for suggesting NPC and guiding the diagnostic workup in occult primary tumors, facilitating earlier diagnosis and reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]