Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia

Abstract microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervi...

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Main Authors: Satoshi Kawai, Takuma Fujii, Iwao Kukimoto, Hiroya Yamada, Naoki Yamamoto, Makoto Kuroda, Sayaka Otani, Ryoko Ichikawa, Eiji Nishio, Yutaka Torii, Aya Iwata
Format: Article
Language:English
Published: Nature Portfolio 2018-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-25310-1
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author Satoshi Kawai
Takuma Fujii
Iwao Kukimoto
Hiroya Yamada
Naoki Yamamoto
Makoto Kuroda
Sayaka Otani
Ryoko Ichikawa
Eiji Nishio
Yutaka Torii
Aya Iwata
author_facet Satoshi Kawai
Takuma Fujii
Iwao Kukimoto
Hiroya Yamada
Naoki Yamamoto
Makoto Kuroda
Sayaka Otani
Ryoko Ichikawa
Eiji Nishio
Yutaka Torii
Aya Iwata
author_sort Satoshi Kawai
collection DOAJ
description Abstract microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.
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spelling doaj.art-fbde035407b74b598073ab70845d7a122022-12-21T22:56:57ZengNature PortfolioScientific Reports2045-23222018-05-018111110.1038/s41598-018-25310-1Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasiaSatoshi Kawai0Takuma Fujii1Iwao Kukimoto2Hiroya Yamada3Naoki Yamamoto4Makoto Kuroda5Sayaka Otani6Ryoko Ichikawa7Eiji Nishio8Yutaka Torii9Aya Iwata10Department of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicinePathogen Genomics Center, National Institute of Infectious Diseases, Musashi-murayamaDepartment of Hygiene, Fujita Health University, School of MedicineLaboratory of Molecular Biology and Histochemistry Joint Research Support Promotion Facility Center for Research Promotion and Support, Fujita Health University, School of MedicineDepartment of Pathology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineDepartment of Obstetrics and Gynecology, Fujita Health University, School of MedicineAbstract microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.https://doi.org/10.1038/s41598-018-25310-1
spellingShingle Satoshi Kawai
Takuma Fujii
Iwao Kukimoto
Hiroya Yamada
Naoki Yamamoto
Makoto Kuroda
Sayaka Otani
Ryoko Ichikawa
Eiji Nishio
Yutaka Torii
Aya Iwata
Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
Scientific Reports
title Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
title_full Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
title_fullStr Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
title_full_unstemmed Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
title_short Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia
title_sort identification of mirnas in cervical mucus as a novel diagnostic marker for cervical neoplasia
url https://doi.org/10.1038/s41598-018-25310-1
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