Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer
Muralidharan Jayaraman1,2,*, Rangasudhagar Radhakrishnan1,*, Cara A. Mathews1,3,*, Mingda Yan1, Sanam Husain4, Katherine M. Moxley1,3, Yong Sang Song5, and Danny N. Dhanasekaran1,2
1 Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
2 Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
3 Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
4 Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
5 Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, S. Korea
* Equal Contribution
Correspondence:
Danny N. Dhanasekaran, email:
Keywords: Endometrial cancer, miRNA, miR-142, miR-15a, therapy response
Received: June 01, 2017 Accepted: June 21, 2017 Published: July 03, 2017
Abstract
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines. Immunohistochemical analysis of the tissue micro array derived from these patients established the functional correlation between the decreased expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR, EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the patients with extended progression-free survival (PFS) ( > 21 months) versus the patients with the PFS of < 21 months indicated increased expression of tumor suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS patients. In addition to defining a specific set of miRNAs and their target genes as potential diagnostic biomarkers, our studies have identified tumor suppressive miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy response in endometrial cancer.
