Background: Pyruvatekinase, which converts phosphoenolpyruvate to pyruvate, is a key enzyme in glucose metabolism and is present in organ-specific isoforms (the L, R, M1, and M2 isoforms). In normal proliferating cells, M2-PK is mainly tetrameric and has a high affinity for phosphoenolpyruvate. In contrast, the M2-PK isoenzyme found in tumor cells is usually dimeric and has a low affinity for phosphoenolpyruvate. For this reason, the dimeric form of M2-PK has been named tumor M2-PK.
Objective: This study evaluated the potential value of fecal, dimeric M2-PK level in differentiating functional from organic colonic disorders as well as its value as a surrogate marker of inflammation in patients with inflammatory bowel disease (IBD) and colorectal cancer (CRC).
Patients and Methods: This prospective study included 60 patients with different colonic disorders, 20 patients with Functional colonic disorders, 20 patients with inflammatory bowel disease (ulcerative colitis & chron‘s disease), and 20 patients with colon cancer. The M2-PK level was measured in all patients using a highly sensitive enzyme – linked immunosorbent assay (ELISA), which allowed the quantitative measurement of tumor M2-PK in stool.
Results: Our study revealed a highly significant increase in tumor M2-PK in the stool samples of those patients with organic colonic disorders (IBD and CRC groups) compared to functional group (IBS). At a cut-off value of 4.2 (U/ml), our overall sensitivity and specificity for organic group over the functional group were 87.5% and 80% respectively. Furthermore, the results of M2-PK levels (U/mL) in our study were shown to be significantly elevated in active, compared to inactive IBD.
Conclusion: In colonic disorders, fecal concentration of tumor M2-PK was a good marker for discrimination of functional from organic colonic conditions (IBD and CRC), with a sensitivity and specificity of 87.5% and 80% respectively. Tumor M2-PK can be used as a tumor marker in screening of colorectal cancer. Dimeric fecal M2-PK has the potential to be an important noninvasive marker of disease activity in IBD.