title: A microRNA survival signature (MiSS) for advanced ovarian cancer.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression primarily through post-transcriptional modification. We tested the hypothesis that miRNA expression is associated with overall survival in advanced ovarian cancer.
  
  
  METHODS
  Cases included newly diagnosed patients with stage III or IV serous ovarian cancer. RNA from a training set of 62 cases was hybridized to an miRNA microarray containing 470 mature human transcripts. Cox Regression was performed to identify miRNAs associated with overall survival. External validation was performed using quantitative RT-PCR miRNA assays in an independent test set of 123 samples. MiRNA targets and associated biologic pathways were predicted in silico.
  
  
  RESULTS
  Of all patients, 80% had high-grade, stage IIIC tumors and 64% underwent optimal cytoreduction. The median survival for the entire cohort was 49±4 months. The training set identified 3 miRNAs associated with survival--miR-337, miR-410, and miR-645. An miRNA signature containing miR-410 and miR-645 was most strongly associated with overall survival in the training set (HR=2.96, 95% CI: 1.51-5.78). This miRNA survival signature (MiSS) was validated in the test set (HR=1.71, 95% CI: 1.05-2.78). The MiSS was independent of FIGO stage and surgical debulking.
  
  
  CONCLUSIONS
  The data suggest that an MiSS that contains miR-410 and miR-645 is negatively associated with overall survival in advanced serous ovarian cancer. This signature, when further validated, may be useful in individualizing care for the ovarian cancer patient. Pathway analyses identify biologically plausible mechanisms.
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Karin K
authors.initials: KK
authors.lastname: Shih
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Qin
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Tanner
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Maria
authors.initials: M
authors.lastname: Bisogna
authors.forename: Fanny
authors.initials: F
authors.lastname: Dao
authors.forename: Narciso
authors.initials: N
authors.lastname: Olvera
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012323:RNA Processing, Post-Transcriptional; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C000598122:MIRN645 microRNA, human; D035683:MicroRNAs