Prognostic Value of PKM2 Expression in de novo Metastatic Colorectal Cancer Patients

Background: Metastatic colorectal cancer (CRC) is considered one of the lethal neoplasms globally. The embryonic M2 isoform of pyruvate kinase (PKM2), a crucial enzyme regulating glycolysis, promotes tumor cell proliferation and metastasis, and is correlated with unfavourable outcomes among several cancers, including CRC. Methods: This prospective cohort study included 80 de novo metastatic CRC patients at the Medical Oncology Department, South Egypt Cancer Institute (SECI), Assiut University, from June 2022 to June 2024. We analyzed the impact of PKM2 expression, evaluated by immunohistochemistry (IHC), in metastatic CRC patients, and response to first-line oxaliplatin-based chemotherapy regimens and survival outcomes in the form of progression-free survival (PFS) and overall survival (OS). Result: The median age of the studied cases was 47 ys, 42 (52.5%) were male, and 54 (67.5%) were left-sided. Our results revealed a statistically significant association between high PKM2 IHC expression and lower overall response rate (ORR), P = 0.001. After a median follow-up time of 13 months(ms), this translated into a statistically significant association between the high PKM2 IHC expression group and lower PFS and OS (6ms vs 10ms; P = 0.008), (12ms vs. 17ms; P = 0.008), respectively. Conclusion: Our results concluded that PKM2 IHC expression was one of the independent prognostic factors for OS. This supports the consideration of PKM2 as a promising molecular target for therapeutic strategies in CRC management.