title: Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.
abstract: BACKGROUND
  A deregulated energy metabolism is a hallmark of malignant disease that offers possible future targets for treatment. We investigated the prognostic value of the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase type M2 (PKM2), mitochondrial β-F1-ATPase (ATP5B) and the bioenergetic cellular (BEC) index in advanced ovarian cancer.
  
  
  METHODS
  Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 met the eligibility criteria; stage IIC-IV, serous or endometrioid subtype, specimens containing ≥ 50% tumor cells and patients receiving platinum-based chemotherapy. An adequate amount of mRNA could be extracted in all but one case, with a resultant study population of 56 patients. Eighty-six percent of cases had serous tumors, and 93% were grade 2-3. GAPDH, PKM2 and ATP5B mRNA- and protein expression was assessed by real-time PCR and immunohistochemistry. We estimated the association with platinum-free interval (PFI) and overall survival (OS) by Cox proportional hazards models. Median follow-up was 60 months.
  
  
  RESULTS
  High GAPDH mRNA levels (HR 2.1, 95% CI 1.0-4.5) and low BEC-index (HR 0.47, 95% CI 0.23-0.95) were both independently associated with shorter PFI. Median PFI for patients with high GAPDH mRNA was 5.0 months compared to 10.1 months for low expression cases (p = 0.031). Similarly, median PFI for patients with low BEC-index based on mRNA was 5.3 months compared to 9.8 months for high BEC-index cases (p = 0.028).
  
  
  CONCLUSIONS
  High GAPDH or low BEC-index mRNA expression indicate early disease progression in advanced serous ovarian cancer.
authors.affiliation: Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden. elisabet.hjerpe@karolinska.se.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Hjerpe
authors.forename: Suzanne
authors.initials: S
authors.lastname: Egyhazi Brage
authors.forename: Joseph
authors.initials: J
authors.lastname: Carlson
authors.forename: Marianne
authors.initials: M
authors.lastname: Frostvik Stolt
authors.forename: Kjell
authors.initials: K
authors.lastname: Schedvins
authors.forename: Hemming
authors.initials: H
authors.lastname: Johansson
authors.forename: Maria
authors.initials: M
authors.lastname: Shoshan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Avall-Lundqvist