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DNA methylation biomarkers for head and neck squamous cell carcinoma

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posted on 2018-08-10, 14:27 authored by Chongchang Zhou, Meng Ye, Shumin Ni, Qun Li, Dong Ye, Jinyun Li, Zhisen Shen, Hongxia Deng

DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients.

Funding

This research was supported by grants from the Medical and Health Research Project of Zhejiang Province (No. 2013KYB231; No.2014KYB229; No. 2017KY133; No.2018RC063); Zhejiang Provincial Natural Science Foundation of China (No. LY16H160005; No. LY16H160003), the Medical Association Clinical Research Project Funding of Zhejiang Province (No. 2015ZYC-A49), the Project of Scientific Innovation Team of Ningbo (No. 2015B11050; No.2012B82019), Ningbo Social Developmental Key Research Project (No.2012C5015), Medical and Health Training Project of Zhejiang Province (No.2014PYA017),Ningbo Natural Science Foundation (No.2012A610208; No. 2015A610221 and 2017A610236) and the Ningbo Health Branding Subject Fund (No.PPXK2018-02).

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