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Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.
Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden.
Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden.
Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden.
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2013 (English)In: BMC Clinical Pathology, ISSN 1472-6890, E-ISSN 1472-6890, Vol. 113, no 30Article in journal (Refereed) Published
Abstract [en]

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
BioMed Central, 2013. Vol. 113, no 30
Keyword [en]
Metabolic markers, GAPDH, PKM2, ATP5B, BEC, Ovarian cancer, Immunohistochemistry, Real-time PCR
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-116608DOI: 10.1186/1472-6890-13-30PubMedID: 24252137Scopus ID: 2-s2.0-84887705174OAI: oai:DiVA.org:liu-116608DiVA: diva2:798974
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04Bibliographically approved

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Åvall-Lundqvist, Elisabeth

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