Detection of high-grade neoplasia in air-dried cervical PAP smears by a microRNA-based classifier
| Autor: | Nikolay N. Kolesnikov, Andrey A. Mikhetko, Sergei A. Glushkov, Anastasia Malek, Mikhail K. Ivanov, Roman Samsonov, Polina A. Arkhangelskaya, Igor Berlev, S. E. Titov, Elena V. Bakhidze, Victoria V. Dzyubenko |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology cervical cancer Uterine Cervical Neoplasms Cervix Uteri 0302 clinical medicine Papillomaviridae human papillomavirus Cervical screening biology microRNA General Medicine Articles Viral Load Prognosis normalization Oncology 030220 oncology & carcinogenesis Female Squamous Intraepithelial Lesions of the Cervix medicine.symptom Viral load Papanicolaou Test Adult medicine.medical_specialty cervical intraepithelial neoplasia Malignancy Cervical intraepithelial neoplasia Lesion 03 medical and health sciences medicine Biomarkers Tumor Humans Vaginal Smears business.industry Papillomavirus Infections Case-control study biology.organism_classification medicine.disease Uterine Cervical Dysplasia MicroRNAs 030104 developmental biology ROC Curve Case-Control Studies DNA Viral business Follow-Up Studies |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Recent studies have shown that changes in the expression levels of certain microRNAs correlate with the degree of severity of cervical lesions. The aim of the present study was to develop a microRNA-based classifier for the detection of high-grade cervical intraepithelial neoplasia (CIN ≥2) in cytological samples from patients with different high-risk human papillomavirus (HR-HPV) viral loads. For this purpose, raw RT-qPCR data for 25 candidate microRNAs, U6 snRNA and human DNA in air-dried PAP smears from 174 women with different cervical cytological diagnoses, 144 of which were HR-HPV-positive [40 negative for intraepithelial lesion or malignancy (NILM), 34 low-grade squamous intraepithelial lesions (L-SIL), 57 high-grade squamous intraepithelial lesions (H-SIL), 43 invasive cancers], were statistically processed. The expression level changes of various individual microRNAs were found to be significantly correlated with the cytological diagnosis but the statistical significance of this correlation was critically dependent on the normalization strategy. We developed a linear classifier based on the paired ratios of 8 microRNA concentrations and cellular DNA content. The classifier determines the dimensionless coefficient (DF value), which increases with the severity of cervical lesion. The high- and low-grade CINs were better distinguished by the microRNA classifier than by the measurement of individual microRNA levels with the use of traditional normalization methods. The diagnostic sensitivity of detecting high-grade lesions (CIN ≥2) with the developed microRNA classifier was 83.4%, diagnostic specificity 81.2%, ROC AUC=0.913. The analysis can be performed with the same nucleic acid preparation as used for HPV testing. No statistically significant correlation of the DF value and HR-HPV DNA load was found. The DF value and the HR HPV presence and viral DNA load may be regarded as independent criteria that can complement each other in molecular screening for high-grade cervical intraepithelial neoplasia. Although it has several limitations, the present study showed that the small-scale analysis of microRNA signatures performed by simple PCR-based methods may be useful for improving the diagnostic/prognostic value of cervical screening. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|