Oncotarget

Research Papers:

The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2

Yunyan Gu, Mengmeng Zhang, Fuduan Peng, Lei Fang, Yuanyuan Zhang, Haihai Liang, Wenbin Zhou, Lu Ao and Zheng Guo _

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Oncotarget. 2015; 6:2397-2406. https://doi.org/10.18632/oncotarget.2963

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Abstract

Yunyan Gu1,*, Mengmeng Zhang1,*, Fuduan Peng1, Lei Fang4, Yuanyuan Zhang1, Haihai Liang3, Wenbin Zhou1, Lu Ao1,2 and Zheng Guo1,2

1 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

2 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China

3 Department of Pharmacology, Harbin Medical University, Harbin, China

4 Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China

* These authors contributed equally to this work

Correspondence:

Zheng Guo, email:

Yunyan Gu, email:

Keywords: miRNAs, BRCA1, BRCA2, Prognosis, Ovarian Cancer

Received: October 23, 2014 Accepted: December 10, 2014 Published: December 11, 2014

Abstract

Ovarian cancer patients carrying alterations (i.e., germline mutations, somatic mutations, hypermethylations and/or deletions) of BRCA1 or BRCA2 (BRCA1/2) have a better prognosis than BRCA1/2 alteration non-carriers. However, patients with wild-type BRCA1/2 may also have a favorable prognosis as a result of other mechanisms that remain poorly elucidated, such as the deregulation of miRNAs. We therefore sought to identify BRCA1/2-directed miRNA signatures that have prognostic value in ovarian cancer patients with wild-type BRCA1/2 and study how the deregulation of miRNAs impacts the prognosis of patients treated with platinum-based chemotherapy. By analyzing multidimensional datasets of ovarian cancer patients from the TCGA data portal, we identified three miRNAs (hsa-miR-146a, hsa-miR-148a and hsa-miR-545) that target BRCA1/2 and were associated with overall survival and progression-free survival in patients with wild-type BRCA1/2. By analyzing the expression profiles and Gene Ontology functional enrichment, we found that carriers of BRCA1/2 alterations and patients with miRNA deregulation shared a common mechanism, regulation of the DNA repair-related pathways, that affects the prognosis of ovarian cancer patients. Our work highlights that a proportion of patients with wild-type BRCA1/2 ovarian cancers benefit from platinum-based chemotherapy and that the patients who benefit could be predicted from BRCA1/2-directed miRNA signature.


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