TMEM196 hypermethylation as a novel diagnostic and prognostic biomarker for lung cancer
TMEM196 hypermethylation as a novel diagnostic and prognostic biomarker for lung cancer
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TMEM196 高甲基化作为肺癌的新型诊断和预后生物标志物
DOI：
10.1002/mc.22942
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发表时间：
2019
影响因子：
4.6
通讯作者：
Jin-Yi Liu
中科院分区：
文献类型：
--
作者：
Wen-Bin Liu;Fei Han;Yong-Sheng Huang;Hong-Qiang Chen;Jian-Ping Chen;Dan-Dan Wang;Xiao Jiang;Li Yin;Jia Cao;Jin-Yi Liu
Emerging evidences have revealed tumor‐specific gene methylation is considered to be a promising non‐invasive biomarker for many different types of cancers. This study was determined whetherTMEM196gene hypermethylation and downregulation are considered to be promising biomarkers for early diagnosis and prognosis in lung cancer. Methylation status was detected with methylation‐specific PCR. Kaplan–Meier survival curves and Cox regression analysis were used to determine the significance of prognosis.TMEM196gene was hypermethylated in 68.1% (64/94) of lung cancer tissues, 52.8% (67/127) of plasma and 55.2% (79/143) of sputum samples, but unmethylated (0/50) in normal tissues.TMEM196methylation in plasma and sputum samples was significantly correlated with that in the corresponding paired tumor tissues (r= 0.750,r= 0.880,P <0.001).TMEM196aberrant methylation in cancer tissues, plasma and sputum DNA was significantly associated with age and pathological type (P <0.05).TMEM196high methylation could robustly distinguish lung cancer patients (AUC = 0.905) from normal subjects and patients withTMEM196high methylation have a significantly poorer survival than those with low level from The Cancer Genome Atlas (WilcoxonP <0.001). Multivariate models showedTMEM196methylation is an independent prognostic marker in lung cancer. Furthermore, the overall survival of patients with low TMEM196 expression was significantly poorer than that of TMEM196‐high patients (P< 0.001, log‐rank test). Low TMEM196 expression in tumor tissues was found to predict poorer survival (HR = 3.007; 95%CI, 1.918‐4.714). Our study provided new insights into the clinical importance and potential use of TMEM196 methylation and expression as novel early diagnostic and prognostic biomarkers for human lung cancers.
