The association between methylated <em>CDKN2A</em> and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis

Abstract

BackgroundCervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN), and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power.MethodsWe systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer.ResultsOur results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54–36.06; cancer vs CIN: OR =2.53, 95% CI =1.79–3.5; CIN vs control: OR =9.68, 95% CI =5.82–16.02). The specificity, sensitivity, area under the receiver operating characteristic curve, and diagnostic odds ratio were 0.99 (95% CI: 0.97–0.99), 0.36 (95% CI: 0.28–0.45), 0.93 (95% CI: 0.91–0.95), and 43 (95% CI: 19–98), respectively.ConclusionOur findings indicate that abnormal CDKN2A methylation may be strongly correlated with the pathogenesis of cervical cancer. Our results also demonstrate that CDKN2A methylation might serve as an early detector of cervical cancer. These findings require further confirmation.

Host proteome linked to HPV E7-mediated specific gene hypermethylation in cancer pathways

“…Suppression of these genes by hypermethylation, and a reduction in their protein abundance, possibly promotes carcinogenesis. Notably cancerous cells often express CDKN2A at low levels mostly, in which through gene methylation [27,28].…”

Role of <em>MLH1</em> methylation in esophageal cancer carcinogenesis and its clinical significance

“… 51 Without effective early diagnosis biomarkers and therapeutic strategies, the prognosis of EC is relatively poor, with a 5-year survival rate of <20%, although it may be variable in different histotypes. 52 Aberrant DNA methylation in the TSG promoter has been identified as an important mechanism of tumorigenesis and progression of several cancers, including cervical cancer, 10 oral cancer, 53 and colorectal cancer. 54 In addition, as a relatively early molecular change, aberrant methylation was reported to be a potential biomarker for early cancer diagnosis.…”

“… 8 Encompassing complicated aspects of cancer development, epigenetic modification is considered to have a crucial role in the carcinogenesis of EC. 9 As one of the most important epigenetic alterations, abnormal DNA methylation in the promoter region induces transcriptional silencing of tumor suppressor genes (TSGs) and plays an important role in the progression of several cancers, such as cervical cancer, 10 hepatocellular carcinoma, 11 and head and neck squamous cell carcinoma. 12 In addition, aberrant methylation has been shown to occur early in the progression of precancerous lesions to EC.…”

A fluorometric hybridization assay for detecting and genotyping high-risk human papillomavirus 16 and 18 in archival tissues of cervical specimens

“…During the clinical course of human papillomavirus (HPV) infection, nearly 90% of people infected with high-or low-risk HPV clear the infection within almost 2 years [1,2]. However, persistent infection with high-risk HPV (HR-HPV), especially types 16 and 18 in minority of the individuals, may lead to cervical intraepithelial neoplasia (CIN), which is the precursor lesion of cervical cancer [3]. On the other hand, CIN is considered to progress in severity over time, passing from grade I (CIN1 or mild epithelial dysplasia), over grade II (CIN2 or moderate dysplasia) to grade III (CIN3 or severe dysplasia), and then to invasive carcinoma [4][5][6].…”