Background: Lung cancer is the most common malignant tumor in clinic. The prognosis of advanced patients is poor, and the 5-year survival rate is low. Therefore, early diagnosis becomes the key to improve the prognosis of patients. In recent years, with the development of molecular biology technology, aberrant modification of some driver genes, such as methylation, has become an important method for early diagnosis of lung cancer. The purpose of the present work was to quantitatively evaluate the diagnostic value of abnormal hypermethylation in short state homeobox 2 (SHOX2) promoter region in lung cancer by evidence-based medicine.
Methods: We searched MEDLINE, EMBASE, Ovid, Web of Science and CNKI for literatures related to the relationship between SHOX2 gene promoter hypermethylation and lung cancer. The data of SHOX2 promoter hymethylation in the original study were extracted. The diagnostic sensitivity, specificity and area under receiver operating characteristic (ROC) curve of SHOX2 promoter methylation were calculated.
Results: Finally, 13 publications were included in this meta-analysis, and due to significant statistical heterogeneity among the studies (P<0.05) the data was pooled by random effect model. The diagnostic sensitivity and specificity of SHOX2 promoter hypermethylation in the diagnosis of lung cancer were 0.75 (95%CI: 0.74-0.77) and 0.89 (95%CI: 0.88-0.91), respectively; The positive likelihood ratio value was 6.75 (4.56-9.99), and the negative predictive value was 0.36 (0.25-0.52); The diagnostic odds ratio was 23.16 (11.34-47.31), and the area under the ROC curve was 0.9.
Conclusions: SHOX2 gene promoter hypermethylation is high in serum, broncholavage fluid and pleural effusion of lung cancer patients, which can be used as a biomarker for auxiliary diagnosis of lung cancer.
【中文题目：矮小同源盒基因启动子区域甲基化 诊断肺癌价值的meta分析】 【中文摘要：背景与目的 肺癌是临床上最为常见的恶性肿瘤，晚期患者预后差，5年生存率低，因此早期诊断成为提高患者预后的关键。近年来随着分子生物学技术的发展，一些关键驱动基因的异常修饰如甲基化成为肺癌早期诊断的重要方法。本研究旨在采用循证医学方法量化评价矮小同源盒基因（short stature homeobox 2, SHOX2）启动子区域异常高甲基化诊断肺癌价值。方法 系统检索MEDLINE、EMBASE、Ovid、Web of Science、中国期刊全文数据库（CNKI）中涉及SHOX2基因启动子区域甲基化与肺癌关系的相关文献，并根据纳入与排除标准进行文献筛选。提取原始研究中SHOX2启动子甲基化相关数据，计算以SHOX2启动子甲基化为参考诊断肺癌的敏感性、特异性及受试者工作特征曲线（receiver operating characteristic curve, ROC）下面积。结果 最终纳入本次meta分析的文献13篇，各项研究间存在明显的统计学异质性（P<0.05），数据合并均采用随机效应模型。SHOX2基因启动子甲基化诊断肺癌的敏感性为0.75（95%CI: 0.74-0.77）、特异性为0.89（95%CI: 0.88-0.91）；阳性预测值为6.75（4.56-9.99），阴性预测值为0.36（0.25-0.52）；诊断优势比为23.16（11.34-47.31），ROC曲线下面积为0.9。结论 SHOX2基因启动子高甲基化在肺癌患者血清、支气管灌洗液和胸腔积液中发生率均较高，可作为辅助诊断肺癌的生物学标志物。 】 【中文关键词：肺肿瘤；SHOX2基因；启动子；甲基化；Meta分析】.
Keywords: Lung neoplasms; Meta-analysis; Methylation; Promoter; SHOX2 gene.