Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.
2013 (English)In: BMC clinical pathology, ISSN 1472-6890, Vol. 13, no 1, 30- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 13, no 1, 30- p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:liu:diva-116608DOI: 10.1186/1472-6890-13-30PubMedID: 24252137OAI: oai:DiVA.org:liu-116608DiVA: diva2:798974