Zhou Chongchang, Li Jinyun, Li Qun
Department of Otorhinolaryngology Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo 315040, Zhejiang, China.
Department of Medical Oncology, Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang, China.
Oncotarget. 2017 Jul 25;8(30):50071-50083. doi: 10.18632/oncotarget.18412.
CDKN2A is a tumor suppressor gene and is frequently inactivated in human cancers by hypermethylation of its promoter. However, the role and diagnostic value of CDKN2A methylation in esophageal cancer (EC) remains controversial. Therefore, we performed a meta-analysis, including data from 42 articles (2656 ECs, 612 precancerous lesions, and 2367 controls). A significant increase in the frequency of CDKN2A methylation was identified during EC carcinogenesis: cancer vs. controls, odds ratio (OR) = 12.60 (95 % CI, 8.90-17.85); cancer vs. precancerous lesions, OR = 2.89 (95% CI, 2.20-3.79); and precancerous lesions vs. controls, OR = 7.38, 95% (CI, 4.31-12.66). CDKN2A promoter methylation was associated with EC tumor grade (OR = 1.79; 95% CI, 1.20-2.67) and clinical stage (OR = 2.56; 95% CI, 1.33-4.92). Additionally, the sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) for diagnosis of EC based on CDKN2A methylation were 0.52 (95% CI, 0.44-0.59), 0.96 (95% CI, 0.93-0.98), and 0.83 (95% CI, 0.79-0.86), respectively. AUCs for blood and tissue sample subgroups were 0.90 and 0.82, respectively. Our findings indicate that CDKN2A methylation has a vital role in EC tumorigenesis and could be a biomarker for early diagnosis of EC.
CDKN2A是一种肿瘤抑制基因，在人类癌症中其启动子常因高甲基化而失活。然而，CDKN2A甲基化在食管癌（EC）中的作用和诊断价值仍存在争议。因此，我们进行了一项荟萃分析，纳入了42篇文章的数据（2656例食管癌、612例癌前病变和2367例对照）。在食管癌发生过程中，CDKN2A甲基化频率显著增加：癌症与对照相比，优势比（OR）=12.60（95%可信区间，8.90 - 17.85）；癌症与癌前病变相比，OR = 2.89（95%可信区间，2.20 - 3.79）；癌前病变与对照相比，OR = 7.38，95%（可信区间，4.31 - 12.66）。CDKN2A启动子甲基化与食管癌肿瘤分级（OR = 1.79；95%可信区间，1.20 - 2.67）和临床分期（OR = 2.56；95%可信区间，1.33 - 4.92）相关。此外，基于CDKN2A甲基化诊断食管癌时，其敏感性、特异性和汇总受试者工作特征曲线下面积（AUC）分别为0.52（95%可信区间，0.44 - 0.59）、0.96（95%可信区间，0.93 - 0.98）和0.83（95%可信区间，0.79 - 0.86）。血液和组织样本亚组的AUC分别为0.90和0.82。我们的研究结果表明，CDKN2A甲基化在食管癌发生中起重要作用，可能是食管癌早期诊断的生物标志物。
