Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers

作     者：Wanxue Xu Mengyao Xu Longlong Wang Wei Zhou Rong Xiang Yi Shi Yunshan Zhang Yongjun Piao 

作者机构：School of MedicineNankai UniversityTianjinChina Tianjin Key Laboratory of Human Development and Reproductive RegulationNankai University Affiliated Hospital of Obstetrics and GynecologyTianjinChina Reproductive Medical CenterNankai University Affiliated Hospital of Obstetrics and GynecologyTianjinChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2019年第4卷第1期

页      面：116-126页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China(61802209,81772974) a project funded by the China Postdoctoral Science Foundation(BS000098) the Fundamental Research Funds of the Central Universities,Nankai University(63181329,63191422) 

主　　题：cervical diagnosis specificity 

摘      要：Cervical cancer is the leading cause of death among women with cancer ***,we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation *** first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene *** DNA methylation profiles of 12 types of cancers,including cervical cancer,were used to generate a candidate set,and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate ***,we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal *** methylation was negatively correlated with the local regulation of gene *** the distant regulation of gene expression,the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression,while the methylation of hypomethylated genes was more likely to be positively correlated with gene ***,we identified four cervical cancer-specific methylation markers,cg07211381(RAB3C),cg12205729(GABRA2),cg20708961(ZNF257),and cg26490054(SLC5A8),with 96.2%sensitivity and 95.2%specificity by using the tenfold cross-validation of TCGA *** four markers could distinguish tumors from normal tissues with a 94.2,100,100,and 100%AUC in four independent validation sets from the GEO ***,our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.