Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer

Abstract

Background: Expression of the dimeric M2 isoenzyme of pyruvate kinase, termed Tumor M2-PK, is increased in some human cancers. This study evaluates the potential role of pre-operative Tumor M2-PK as a marker of prognosis in patients with pancreatic malignancy. Methods: Seventy-three consecutive patients with a clinical diagnosis of pancreatic or peri-ampullary cancer were enrolled. Their median (range) age was 66 (23-83) years. Pre-operative samples of venous blood were taken for analysis of Tumor M2-PK. The full study protocol was approved by the North West Research Ethics Committee (protocol number 06/MRE08/69). Results: The mean (standard deviation) plasma Tumor M2-PK in pancreatic/peri-ampullary malignancy was 60.3 (106.5) U/ml and 22 U/ml (SD: 12 U/ml) in benign disease (p < 0.001). Multivariate Cox regression analysis showed that Tumor M2-PK (> 27 U/mL), Ca19-9 (> 39 U/ml), resection status, and disease stage were associated with poorer survival. Tumor M2-PK values greater than 27 U/ml were associated with inferior survival compared to those with lower values (hazard ratio 2.049, significantly increased risk of death, p = 0.042). Conclusion: This preliminary study shows that an elevated level of Tumor M2-PK (with a cutoff threshold of 27 U/mL) measured pre-operatively is associated with poorer prognosis in patients with pancreatic and peri-ampullary cancer.