title: Circulating U2 small nuclear RNA fragments as a novel diagnostic tool for patients with epithelial ovarian cancer.
abstract: BACKGROUND
  Ovarian cancer is the leading cause of death among malignancies in women. Despite advances in treatment, >50% of patients relapse. For disease monitoring, the identification of a blood-based biomarker would be of prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or small nuclear RNA (snRNA), have been suggested as biomarkers for noninvasive cancer diagnosis. In the present study, we sought to identify differentially expressed miRNA/snRNA in sera of ovarian cancer patients and investigate their potential to aid in therapy monitoring.
  
  
  METHODS
  miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n = 119) by reverse-transcription quantitative PCR.
  
  
  RESULTS
  Abundance of U2-1 snRNA fragment (RNU2-1f) was significantly increased in sera of ovarian cancer patients (P < 0.0001) and paralleled International Federation of Gynecology and Obstetrics stage as well as residual tumor burden after surgery (P < 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated with radiographic response after chemotherapy and with platinum resistance (P = 0.0088 and P = 0.0015, respectively). Interestingly, according to the RNU2-1f abundance dynamics, persistent RNU2-1f positivity before surgery and after chemotherapy identified a subgroup of patients with high risk of recurrence and poor prognosis.
  
  
  CONCLUSIONS
  This is the first report to suggest that a circulating snRNA can serve as an auxiliary diagnostic tool for monitoring tumor dynamics in ovarian cancer. Our results provide a rationale to further investigate whether this high-risk patient group may benefit from additional therapies that are directly applied after chemotherapy.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital of Essen, Germany;
authors.forename: Jan Dominik
authors.initials: JD
authors.lastname: Kuhlmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Baraniskin
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Frank
authors.initials: F
authors.lastname: Mosel
authors.forename: Maren
authors.initials: M
authors.lastname: Bredemeier
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
mesh_terms: D015415:Biomarkers / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D046228:Microarray Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis*; D011379:Prognosis; D012342:RNA, Small Nuclear / Q000097:blood* / Q000235:genetics; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D012342:RNA, Small Nuclear; C405484:U2 small nuclear RNA