Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia
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ORIGINAL ARTICLE
Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia Tímea Szekerczés 1 & Ádám Galamb 2 & Norbert Varga 3 & Márta Benczik 4,5 & Adrienn Kocsis 5 & Krisztina Schlachter 1,6 & András Kiss 1 & Nándor Ács 2 & Zsuzsa Schaff 1 & Csaba Jeney 7 & Gábor Lendvai 1 & Gábor Sobel 2 Received: 6 February 2020 / Accepted: 11 June 2020 # The Author(s) 2020
Abstract Cervical cancer is a common malignant tumor worldwide ranking fourth in incidence and mortality among females, which was reduced significantly by cytology screening and human papilloma virus (HPV) DNA testing. The specificity of cytology is high; however, the sensitivity is low, in contrast to the HPV DNA testing. Despite the success of these measures, new biomarkers are still considered to aim increasing sensitivity and specificity of screening and diagnosis. Significant alterations in microRNA (miRNA) expression have been detected in several cancers with variable consistency. To investigate the stratification role of miRNAs between normal epithelium and cervical intraepithelial neoplasia (CIN2–3), we screened the expression of 667 miRNAs to identify significant markers (n = 10), out of them 9 miRNAs were applied in the study (miR-20b, −24, −26a, −29b, −99a, −100, −147, −212, −515-3p) along with RNU48 and U6 as the references. To benchmark the miRNAs, 22 paired (tumor-free and tumor tissue pairs) laser microdissection-obtained cervical formalin fixed, paraffin embedded tissue samples were assayed. The expression of miR-20b was 2.4 times higher in CIN2–3 samples as compared to normal tissues (p < 0.0001). In the HPV16-positive subsets of the samples (n = 13), miR-20b showed 2.9-times elevation (p < 0.001), whereas miR-515 was 1.15-times downregulated (p < 0.05) in CIN2–3 as compared to normal tissue. These results suggest the potential value of miR20b as a statification biomarker in order to differentiate neoplastic and non-tumorous cases. Keywords Cervical cancer . Cervical intraepithelial neoplasia (CIN) . microRNA . Human papilloma virus
Introduction Tímea Szekerczés, Ádám Galamb, Gábor Lendvai and Gábor Sobel contributed equally to this work. * Gábor Sobel [email protected] 1
2nd Department of Pathology, Semmelweis University, Budapest Hungary
2
Department of Obstetrics and Gynecology, Semmelweis University, Üllői 78/A Budapest 1082 Hungary
3
Nuffield Department of Clinical Neurosciences, Sleep & Circadian Neuroscience Institute, Oxford University, Oxford UK
4
SYNLAB Hungary Kft, Budapest Hungary
5
NEUMANN Diagnostics Ltd, Budapest Hungary
6
Present address: Department of Pathology, National Institute of Oncology, Budapest Hungary
7
Department of Microsystems Engineering, Albert-Ludwigs University, Freiburg Germany
Cervical cancer is a common malignant tumor worldwide among females regarding both incidence and mortality, ranking fourth after breast, lung, and colorectal cancer with an estimated 570,000 new cases yearly and 311,000 cancer related deaths in 2018 according to GLOBOCAN sources [1]. There is, however,
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