Early diagnostic value of methylation in promoter region of FAM19A4, PAX1 and miRNA124-2 in cervical lesions

Abstract

Background and purpose: At present, there have been many reports on the study of methylation in cervical lesions, however it is still not clinically practical as a diagnostic and shunting index of cervical lesions. In this study, we intended to investigate the early diagnostic value of FAM19A4, PAX1 and miRNA124-2 methylation in promoter region in the progression of cervical lesions. Methods: A total of 129 liquid-based cytology specimens of different grades of cervical lesions diagnosed in the Third Affiliated Hospital of Zhengzhou University from Mar. 2020 to Mar. 2022. Methylation specific PCR (MSP) was used to detect the methylation changes of FAM19A4, PAX1 and miRNA124-2 genes in different cervical lesions. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of methylation changes of the three genes in cervical lesions. This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (No. 2023-135-01). Results: All the specimens were collected and divided into 4 groups according to the histological results: 42 cases of no intraepithelial lesions or malignant lesions (NILM), 28 cases of low grade squamous intraepithelial lesion (LSIL), 36 cases of high grade squamous intraepithelial lesion (HSIL), 23 cases of squamous cervical cancer (SCC). With the increase in the level of cervical lesions, FAM19A4, PAX1 and miRNA124-2 gene methylation detection rates increased gradually, and the differences were statistically significant (P<0.05). The methylation detection rates of FAM19A4, PAX1 and miRNA124-2 in HSIL group were 81.2%, 80.5% and 71.8%, respectively, and the methylation detection rates of three genes in SCC group were up to 100.0%. Cytological diagnosis of cervical cancer showed the area under curve (AUC) was 0.731, with a sensitivity and a specificity of 65.9% and 80.4%, respectively. When FAM19A4, PAX1 and miRNA124-2 were used alone to diagnose HSIL+ (HSIL and SCC), PAX1 methylation had the highest diagnostic efficiency, and the AUC was 0.925, with a sensitivity and a specificity of 92.8% and 87.3%. When the diagnosis was made in pairs, the AUC of FAM19A4 combined with PAX1 in the diagnosis of HSIL+ was 0.930, with a sensitivity and a specificity of 95.7% and 87.1%, respectively. The AUC of FAM19A4 combined with miRNA124-2 in the diagnosis of HSIL+ was 0.895, with a sensitivity and a specificity of 97.6% and 85.7%, respectively. The AUC of PAX1 combined with miRNA124-2 in the diagnosis of HSIL+ was 0.928, with a sensitivity and a specificity of 95.7% and 89.1%, respectively. When the PAX1 and FAM19A4 combined with miRNA124-2 in the diagnosis of HSIL+, the AUC was 0.928, with a sensitivity and a specificity of 100.0% and 81.8%, respectively. Conclusion: The methylation of the promoter regions of the FAM19A4, PAX1 and miRNA124-2 genes demonstrates high sensitivity and specificity in diagnosing cervical lesions, indicating the potential for becoming novel indicators for early diagnosis of cervical lesions.

Keywords

• |fam19a4|pax1|mirna124-2|methylation|cervical lesion