title: The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma.
abstract: Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a* and miR-30e* were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a* and miR-30e*, and showed a significant upregulation in type II patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a* and miR-30e* genes. Further analysis using leave‑one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a* and miR-30e* can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a* and miR-30e* coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.
authors.affiliation: Laboratory Center, Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.
authors.forename: Lv
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, P.R. China.
authors.forename: Zhenyun
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.
authors.forename: Ruomeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Obstetrics and Gynecology Hospital, Dalian, P.R. China.
authors.forename: Tie
authors.initials: T
authors.lastname: Bi
authors.affiliation: Obstetrics and Gynecology Hospital, Dalian, P.R. China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, P.R. China.
authors.forename: Henan
authors.initials: H
authors.lastname: Zhao
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics; D000328:Adult; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055815:Young Adult
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C546086:MIRN30b microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc