title: Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas.
abstract: This study aimed to determine the expression profiles of microRNAs (miRNAs) in endometrial serous adenocarcinoma and to examine the association between miRNA expression and clinical outcomes. Twenty-one patients diagnosed with endometrial serous adenocarcinoma between January 2001 and December 2006 were enrolled. miRNA expression profiles were examined using miRNA microarray and qRT-PCR. miRNA expression levels were correlated with clinicopathological variables and survival rates. A total of 120 miRNAs were differentially expressed in endometrial serous adenocarcinoma compared to normal endometria. Of these, 54 miRNAs were down-regulated (>2-fold), including miR-101, miR-10b*, miR-152, and miR-29b, and the remainder were up-regulated (>2-fold), including miR-200a, miR-200b, and miR-205. Decreased expression of miR-10b*, miR-29b, and miR-455-5p was correlated with vascular invasion (P = 0.048, P = 0.013, and P = 0.032, respectively). Univariate analysis revealed that lower expression of miR-101, miR-10b*, miR-139-5p, miR-152, miR-29b, and miR-455-5p was significantly correlated with poor overall survival (P < 0.05), and reduced expression of miR-152, miR-29b, and miR-455-5p was significantly correlated with poor disease-free survival (P < 0.05). Multivariate analysis demonstrated that decreased expression of miR-152 (P = 0.021) was a statistically independent risk factor for overall survival, and decreased expression levels of miR-101 (P = 0.016) and miR-152 (P = 0.010) were statistically independent risk factors for disease-free survival. In addition, transfection of miR-101 or miR-152 precursors into an endometrial serous carcinoma cell line inhibited cell growth (P < 0.0001 and P = 0.01, respectively). Moreover, strong positive immunoreactivity of cyclooxygenase-2 (COX-2) was significantly correlated with down-regulation of miR-101 (P = 0.035). These findings suggest that the dysregulation of miRNAs is associated with the poor prognosis in endometrial serous adenocarcinoma patients.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan. e-hiroki@mail.tains.tohoku.ac.jp
authors.forename: Eri
authors.initials: E
authors.lastname: Hiroki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Suzuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D035683:MicroRNAs; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human