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

Mikhail K. Ivanov, Sergei E. Titov, Victoria V. Dzyubenko, Sergei A. Glushkov, Sergey E. Krasilnikov, Alphiya S. Mansurova, Anastasia V. Malek, Igor V. Berlev, Tatyana S. Prisyazhnaya, Svetlana V. Kuleshova, Anastasia A. Hodkevich, Yury A. Lancuhaj, Tatiana A. Dimitriadi, Eduard F. Agletdinov

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)541-554
Number of pages14
JournalJournal of Molecular Diagnostics
Volume23
Issue number5
DOIs
Publication statusPublished - May 2021

OECD FOS+WOS

  • 3.01.TM PATHOLOGY
  • 1.06 BIOLOGICAL SCIENCES

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