Abstract
468 Background: Tumor cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase (PKM2), which is a key enzyme that regulates aerobic glycolysis in tumor cells. Use of RNA interfering (RNAi) targeting PKM2 significantly inhibits tumor growth when combined with cisplatin in xenograft models. We evaluated the predictive significance of PKM2 in patients with “high” risk stage II or stage III colon cancer treated with oxaliplatin-fluoropyrimidines chemotherapy adjuvant treatment. Methods: FFPE primary tumours from 261 patients with stage II or III colon cancer with colon cancer were analyzed for PKM2 mRNA expression by RT-qPCR. All patients had received adjuvant treatment with an oxaliplatin and fluoropyrimidine combination. Also, match normal mucosas from 50 of these patients have been analyzed. Finally, 50 polyps (20 with low grade dysplasia, 20 high grade dysplasia and 10 serrated adenomas) from non-colon cancer patients were included in the for PKM2 mRNA expression by RT-qPCR. The analysis was performed with a set of primers and probes which amplify only the M2 isoform. Results: PKM2 mRNA expression was significantly higher in tumor areas in comparison with normal mucosa (p=0.001) and low-grade adenomas (p=0.001) as well as in tumors with BRAF mutations (p=0.001). Adenomas with high-grade dysplasia (p=0.002) and serrated adenomas (p=0.001) presented significantly higher PKM2 mRNA expression. Overexpression of PKM2 was associated with significantly lower Disease Free (p=0.018) and Overall Survival (p=0.031). Multivariate analysis revealed PKM2 high mRNA expression as independent prognostic factors for decreased DFS (HR: 2.1, p=0.003) and OS (HR: 1.8, p=0.019). Conclusions: These results provide evidence that the PKM2 mRNA expression could be used as prognostic/predictive marker for disease recurrence in patients with operable colon cancer. Analysis of the PKM2 mRNA expression in patients treated with non-oxaliplatin containing adjuvant treatment is currently performed.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call