Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage markers for early detection of cervical cancer.

Autor: Snoek BC; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Verlaat W; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Babion I; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Novianti PW; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands.; Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Biostatistics, Amsterdam, Netherlands., van de Wiel MA; Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Biostatistics, Amsterdam, Netherlands.; Amsterdam UMC, Vrije Universiteit Amsterdam, Mathematics, Amsterdam, Netherlands., Wilting SM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands.; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands., van Trommel NE; Department of Gynecology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands., Bleeker MCG; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Massuger LFAG; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, Netherlands., Melchers WJG; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands., Sie D; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Heideman DAM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Snijders PJF; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Meijer CJLM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands., Steenbergen RDM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2019 Jan 15; Vol. 144 (2), pp. 372-379. Date of Electronic Publication: 2018 Nov 04.
DOI: 10.1002/ijc.31855
Abstrakt: Offering self-sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self-samples are needed to stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self-samples. Our study is the first to establish genome-wide miRNA profiles in HPV-positive self-samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self-samples. Small RNA sequencing (sRNA-Seq) was conducted to determine genome-wide miRNA expression profiles in 74 HPV-positive self-samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRridge, a penalized method on logistic regression. Six miRNAs were validated by qPCR in 191 independent HPV-positive self-samples. Classification of sRNA-Seq data yielded a 9-miRNA marker panel with a combined area under the curve (AUC) of 0.89 for CIN3 detection. Validation by qPCR resulted in a combined AUC of 0.78 for CIN3+ detection. Our study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected by sRNA-Seq in HPV-positive self-samples. Validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self-samples.
(© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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