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

BMC Clinical Pathology

Elisabeth Åvall-Lundqvist⁴  Maria Shoshan¹  Hemming Johansson⁴  Kjell Schedvins²  Marianne Frostvik Stolt¹  Joseph Carlson³  Suzanne Egyhazi Brage¹  Elisabet Hjerpe⁴ 

[1] Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet, SE-17176, Stockholm, Sweden;Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden;Department of Pathology, Karolinska University Hospital, Stockholm, Sweden;Department of Oncology, Unit for Gynecologic Oncology, Karolinska University Hospital, SE-17176, Stockholm, Sweden

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

Others  :  1084743
DOI  :  10.1186/1472-6890-13-30

 received in 2013-05-29, accepted in 2013-11-13,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Hjerpe et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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