The Role of CADM1 and MAL Promoter Methylation in Inflammation and Cervical Intraepithelial Neoplasia

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Abstract
Aims: This study investigated the presence of human papillomavirus (HPV) infection and the methylation status of the promoters of the cell adhesion molecule 1 ( CADM1 ) gene and T lymphocyte maturation associated protein ( MAL ) gene in patients with cervicitis/inflammation and cervical intraepithelial neoplasia (CIN). Materials and Methods: Cervical specimens ( n = 47) were collected from women with normal cervical cytology ( n = 21) and those with cervical abnormalities ( n = 26). The presence of HPV infection was confirmed by an HPV DNA test and an HPV mRNA test (Aptima HPV test). Methylation levels of the CADM1 and MAL promoters were evaluated by pyrosequencing. Results: Compared with the HPV DNA test, the Aptima HPV test improved specificity from 57% to 70% for the detection of inflammation and/or CIN type 1 (CIN1) or more advanced conditions (CIN1+). The methylation level of the CADM1 and MAL promoters was 1.5 times higher in inflammatory samples, compared with normal cervical cytology ( p < 0.05). Conclusion: Selected 5′-C-phosphate-G-3′ islands within the promoters of the CADM1 and MAL genes were differentially methylated in the inflammatory samples compared with the CIN samples. These results suggested that methylation likely occurred following tissue disruption, and the detection of persistent inflammation might be associated with a higher risk of lesion progression.

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