FAM19A4 and hsa-miR124-2 Double Methylation as Screening for ASC-H- and CIN1 HPV-Positive Women

• Published in: Pathogens (Basel) Vol. 13; no. 4; p. 312
• Main Authors: Peronace, Cinzia, Cione, Erika, Abrego-Guandique, Diana Marisol, Fazio, Marco De, Panduri, Giuseppina, Caroleo, Maria Cristina, Cannataro, Roberto, Minchella, Pasquale
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024; MDPI
• Subjects: Age; ASC-H; Bioinformatics; Biological markers; Biomarkers; Bisulfite; Cancer; Cellular biology; Cervical cancer; CIN1; Communication; Cytology; Deoxyribonucleic acid; Diagnosis; DNA; DNA methylation; double methylation; Gene expression; Genes; Genetic aspects; Genetic testing; Genotypes; Genotyping; Health aspects; Health savings accounts; Human papillomavirus; Infection; Infections; Lesions; Medical screening; Methylation; microRNAs; Oncology, Experimental; Papillomavirus infections; Quality control; Risk factors; Risk management; Screening; Squamous cells; Womens health; Italy; Eastern Europe; United States > US; microRNAs; double methylation; ASC-H; CIN1
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens13040312

The DNA methylation levels of host cell genes increase with the severity of the cervical intraepithelial neoplasia (CIN) grade and are very high in cervical cancer. Our study aims to evaluate FAM19A4 and hsa-miR124-2 methylation in Atypical Squamous cells with high-grade squamous intraepithelial lesions (ASC-H) and in CIN1, defined as low-grade squamous intraepithelial lesions (LSILs) by the Bethesda classification, as possible early warning biomarkers for managing women with high-risk HPV infections (hrHPV). FAM19A4 and hsa-miR124-2 methylation tests were conducted on fifty-six cervical screening samples from a subset of women aged 30-64 years old. Specimens were collected into ThinPrep PreservCyt Solution. Their HrHPV genotype and cytology diagnosis were known. A Qiasure (Qiagen) was used for FAM19A4 and hsa-miR124-2 methylation testing on bisulfite-converted DNA, according to the manufacturer's specifications. The reported results were hypermethylation-positive or -negative. We found that FAM194A4 and hsa-miR124-2 methylation was detected in 75% of ASC-H cases with a persistent infection of hrHPV. A total of 60% of CIN1 lesions were found to be positive for methylation, and 83.3% were when the cytology was CIN2/3. In addition, as a novelty of this pilot study, we found that combined FAM19A4 and hsa-miR124-2 methylation positivity rates (both methylated) were associated with the HPV genotypes 16, 18, and 59 and covered 22 and 25% of ASC-H and CIN1 cases, respectively. The methylation of these two genes, in combination with HPV genotyping, can be used as an early warning biomarker in the management and follow-up of women with ASC-H and CIN1 to avoid their progression to cervical cancer.