Detection of Cervical Lesions and Cancer in Air-Dried Cytologic Smears by Combined Analysis of mRNA and miRNA Expression Levels.

Autor:	Ivanov MK; AO Vector-Best, Novosibirsk, Russia; Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia. Electronic address: ivanovmk@vector-best.ru., Titov SE; AO Vector-Best, Novosibirsk, Russia; Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia., Dzyubenko VV; AO Vector-Best, Novosibirsk, Russia. Electronic address: dzyubenko@vector-best.ru., Glushkov SA; AO Vector-Best, Novosibirsk, Russia., Krasilnikov SE; Novosibirsk Regional Oncology Dispensary, Novosibirsk, Russia., Mansurova AS; Novosibirsk Regional Oncology Dispensary, Novosibirsk, Russia., Malek AV; N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia; Oncosystem Ltd., Moscow, Russia., Berlev IV; N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia; E. Metchnikoff North-Western State Medical University, Saint Petersburg, Russia., Prisyazhnaya TS; E. Metchnikoff North-Western State Medical University, Saint Petersburg, Russia., Kuleshova SV; Polyclinic No. 2, Department of Presidential Affairs of Russian Federation, Moscow, Russia., Hodkevich AA; AO Vector-Best, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia., Lancuhaj YA; Medsanchast-168, Novosibirsk, Russia., Dimitriadi TA; Rostov Medical University, Rostov-on-Don, Russia., Agletdinov EF; AO Vector-Best, Novosibirsk, Russia.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2021 May; Vol. 23 (5), pp. 541-554. Date of Electronic Publication: 2021 Mar 01.
DOI:	10.1016/j.jmoldx.2021.01.016
Abstrakt:	Cervical cancer screening is based on cytologic analysis and high-risk human papillomavirus (HR-HPV) testing, each having their drawbacks. Implementation of new biomarker-based methods may improve screening accuracy. Here, the levels of 25 microRNAs (miRNAs, miRs) and 12 mRNAs involved in cervical carcinogenesis in 327 air-dried Papanicolaou-stained cervical smears from patients with cervical precancerous lesions, cancer, or without the disease were estimated by real-time PCR. Using logistic regression analysis, small-scale miRNA-based, mRNA-based, and combined molecular classifiers were built based on paired ratios of miRNA or mRNA concentrations; their ability to detect high-grade cervical lesions and cancer was then compared. Combined mRNA-miRNA classifiers manifested a better combination of sensitivity and specificity than miRNA- and mRNA-based classifiers. The best classifier, combining miR-375, miR-20, miR-96, CDKN2A, TSP4, and ECM1, predicted high-grade lesions with diagnostic sensitivity of 89.0%, specificity of 84.2%, and a receiver-operating characteristic area under the curve of 0.913. Additionally, in a subsample of the same specimens, the levels of MIR124-2 and MAL promoter methylation, HR-HPV genotypes, and viral loads were analyzed. The relative high-grade lesion risk estimated by the classifier correlated with the frequency of MAL and MIR124-2 methylation but not with the HR-HPV genotype or viral load. The results support the feasibility of cellular biomarker-based methods for cervical screening and patient management. (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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