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Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

ABSTRACT: The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation?specific PCR, semi?quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3?methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.

SUBMITTER: Ni H

PROVIDER: S-EPMC5547962 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

Ni Haifeng H Jiang Bo B Zhou Zhen Z Yuan Xiaoyang X Cao Xiaolin X Huang Guangwu G Li Yong Y

International journal of molecular medicine 20170627 3

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, ...[more]

PMID: 28656302

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Project description:BACKGROUND:Aberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC. METHODS:Data of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network. RESULTS:In total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified. CONCLUSIONS:The data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.

Dataset Information

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

Publications

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

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