Wang Yi, Qin Xiuguang, Wu Jieqing, Qi Bo, Tao Yipeng, Wang Wenju, Liu Fulei, Li Hanchen, Zhao Baosheng
Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
PLoS One. 2014 Sep 17;9(9):e107598. doi: 10.1371/journal.pone.0107598. eCollection 2014.
Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer.
A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively.
Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P<0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P<0.00001).
The results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.
runt相关转录因子3（RUNX3）是转录因子runt结构域家族的成员。新出现的证据表明，RUNX3在包括食管癌在内的几种人类癌症中是一种肿瘤抑制基因。然而，RUNX3启动子甲基化与食管癌之间的关联仍不清楚。在此，我们进行了一项系统综述和荟萃分析，以定量评估RUNX3启动子甲基化对食管癌发病率的影响。
在Medline、Pubmed和Web of Science上对以英文和/或中文撰写的相关研究出版物进行了详细的文献检索。还评估了研究的方法学质量。数据由两名审阅者独立提取和评估。进行汇总数据分析，分别计算并总结优势比（OR）。
对来自9项符合条件研究的558例患者进行了最终分析。结果显示，食管癌中RUNX3甲基化显著高于近端切缘正常鳞状黏膜或食管良性病变（OR = 2.85，CI = 2.01 - 4.05，P < 0.00001）。RUNX3阴性病例（RUNX3未甲基化组）的淋巴结受累、肿瘤大小（T1 - T2与T3 - T4）和组织学分级的发生率显著高于RUNX3阳性病例（OR = 0.25，CI = 0.14 - 0.43，P < 0.00001）。食管腺癌（EAC）中RUNX3甲基化显著高于巴雷特食管（OR = 0.35，CI = 0.20 - 0.59，P < 0.0001）。此外，汇总的总生存期（OS）风险比显示，RUNX3表达降低与食管癌患者较差的生存率相关（HR = 4.31，95% CI = 2.57 - 7.37，P < 0.00001）。
这项荟萃分析的结果表明，RUNX3甲基化与食管癌风险增加、进展以及较差的生存率相关。RUNX3甲基化诱导RUNX3基因失活，在食管癌发生中起重要作用。
