title: Comparative Analysis of Differentially Expressed miRNAs and their Downstream mRNAs in Ovarian Cancer and its Associated Endometriosis.
abstract: OBJECTIVE
  There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs.
  
  
  METHODS
  Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR.
  
  
  RESULTS
  The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression ofmiR-1,miR-133a, andmiR-451were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression ofmiR-141,miR-200a,miR-200c, andmiR-3613were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-κB expression.
  
  
  CONCLUSIONS
  The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC associated with endometriosis.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Richard Licheng
authors.initials: RL
authors.lastname: Wu
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shadan
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Baraa
authors.initials: B
authors.lastname: Alosh
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Kinda
authors.initials: K
authors.lastname: Hayek
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Mhd Fayez
authors.initials: MF
authors.lastname: Daaboul
authors.affiliation: Department of obstetrics and Gynecology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Winer
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
keywords: Endometriosis; FFPE; NF-κB; Ovarian cancer; PTEN; miRNA
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