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Article

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions

1
Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
2
Department of Pathology, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain
3
ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain
*
Author to whom correspondence should be addressed.
These authors equally contributed to the work.
Int. J. Mol. Sci. 2019, 20(9), 2262; https://doi.org/10.3390/ijms20092262
Received: 30 March 2019 / Revised: 2 May 2019 / Accepted: 7 May 2019 / Published: 7 May 2019
(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)
Background: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. Design: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. Results: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. Conclusions: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN. View Full-Text
Keywords: CADM1; MAL; miR124; methylation; HSIL CADM1; MAL; miR124; methylation; HSIL
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MDPI and ACS Style

del Pino, M.; Sierra, A.; Marimon, L.; Martí Delgado, C.; Rodriguez-Trujillo, A.; Barnadas, E.; Saco, A.; Torné, A.; Ordi, J. CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions. Int. J. Mol. Sci. 2019, 20, 2262. https://doi.org/10.3390/ijms20092262

AMA Style

del Pino M, Sierra A, Marimon L, Martí Delgado C, Rodriguez-Trujillo A, Barnadas E, Saco A, Torné A, Ordi J. CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions. International Journal of Molecular Sciences. 2019; 20(9):2262. https://doi.org/10.3390/ijms20092262

Chicago/Turabian Style

del Pino, Marta, Adriana Sierra, Lorena Marimon, Cristina Martí Delgado, Adriano Rodriguez-Trujillo, Esther Barnadas, Adela Saco, Aureli Torné, and Jaume Ordi. 2019. "CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions" International Journal of Molecular Sciences 20, no. 9: 2262. https://doi.org/10.3390/ijms20092262

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