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Open Access Research article

Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer

Elisabet Hjerpe1*, Suzanne Egyhazi Brage2, Joseph Carlson3, Marianne Frostvik Stolt2, Kjell Schedvins4, Hemming Johansson1, Maria Shoshan2 and Elisabeth Åvall-Lundqvist1

Author Affiliations

1 Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden

2 Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden

3 Department of Pathology, Karolinska University Hospital, Stockholm, Sweden

4 Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden

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BMC Clinical Pathology 2013, 13:30  doi:10.1186/1472-6890-13-30

Published: 19 November 2013

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.

Keywords:
Metabolic markers; GAPDH; PKM2; ATP5B; BEC; Ovarian cancer; Immunohistochemistry; Real-time PCR