MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer

Abstract Background Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient...

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Main Authors: Sunyoung Park, Kiyoon Eom, Jungho Kim, Hyeeun Bang, Hye-young Wang, Sungwoo Ahn, Geehyuk Kim, Hyoungsoon Jang, Sunghyun Kim, Dongsup Lee, Kwang Hwa Park, Hyeyoung Lee
Format: Article
Language:English
Published: BMC 2017-09-01
Series:BMC Cancer
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Online Access:http://link.springer.com/article/10.1186/s12885-017-3642-5
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author Sunyoung Park
Kiyoon Eom
Jungho Kim
Hyeeun Bang
Hye-young Wang
Sungwoo Ahn
Geehyuk Kim
Hyoungsoon Jang
Sunghyun Kim
Dongsup Lee
Kwang Hwa Park
Hyeyoung Lee
author_facet Sunyoung Park
Kiyoon Eom
Jungho Kim
Hyeeun Bang
Hye-young Wang
Sungwoo Ahn
Geehyuk Kim
Hyoungsoon Jang
Sunghyun Kim
Dongsup Lee
Kwang Hwa Park
Hyeyoung Lee
author_sort Sunyoung Park
collection DOAJ
description Abstract Background Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. Methods The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. Results MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001). Conclusions There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.
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spelling doaj.art-86a286c9674e4cb2b24ffb519a7ebe372022-12-21T23:21:54ZengBMCBMC Cancer1471-24072017-09-011711810.1186/s12885-017-3642-5MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancerSunyoung Park0Kiyoon Eom1Jungho Kim2Hyeeun Bang3Hye-young Wang4Sungwoo Ahn5Geehyuk Kim6Hyoungsoon Jang7Sunghyun Kim8Dongsup Lee9Kwang Hwa Park10Hyeyoung Lee11Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityOptipharm M&D, Inc., Wonju Eco Environmental Technology CenterOptipharm M&D, Inc., Wonju Eco Environmental Technology CenterDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of PusanDepartment of Clinical Laboratory Science, Hyejeon CollegeDepartment of Pathology, Wonju College of Medicine, Yonsei University Wonju College of MedicineDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei UniversityAbstract Background Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. Methods The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. Results MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001). Conclusions There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.http://link.springer.com/article/10.1186/s12885-017-3642-5Cervical cancermicroRNAHPV E6/E7RT-qPCRMolecular diagnosis
spellingShingle Sunyoung Park
Kiyoon Eom
Jungho Kim
Hyeeun Bang
Hye-young Wang
Sungwoo Ahn
Geehyuk Kim
Hyoungsoon Jang
Sunghyun Kim
Dongsup Lee
Kwang Hwa Park
Hyeyoung Lee
MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
BMC Cancer
Cervical cancer
microRNA
HPV E6/E7
RT-qPCR
Molecular diagnosis
title MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
title_full MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
title_fullStr MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
title_full_unstemmed MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
title_short MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
title_sort mir 9 mir 21 and mir 155 as potential biomarkers for hpv positive and negative cervical cancer
topic Cervical cancer
microRNA
HPV E6/E7
RT-qPCR
Molecular diagnosis
url http://link.springer.com/article/10.1186/s12885-017-3642-5
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