Yang Lin, Feng Lv, Fangfang Liu

 Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital

Objective:Pyruvatekinase M2 (PKM2) is the key enzyme in Warburg effect and was reported to be involved in metabolic pathways of tumor cells response to chemotherapeutic drugs recently. In this study, we examined the correlation between the expression of PKM2 and the sensitivity of primary breast cancer cells to anticancer drugs. Method: PKM2 expression was studied by immunohistochemistry in 296 cases of invasive breast cancer patients' biopsy, and all the patients had collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to detect in vitro chemosensitivity after surgery. Result: We found high PKM2 expression significantly associated with good sensitivity to epirubicin (EPI) (P=0.019) and 5-fluorouracil (5-Fu) (P=0.009). Then we used a small neoadjuvant chemotherapy cases to confirm that the higher PKM2 expression, the better pathological response to therapy was obtained in patients treated with EPI-based or EPI plus 5-Fu chemotherapy regimens. Although univariate and multivariate analysis indicated high PKM2 was a poor independent predictor of progression free survival (PFS) (P=0.003) and overall survival (OS) (P=0.008)in human breast cancer, in PKM2 high expression cohort alone patients received EPI-based or EPI plus 5-Fu chemotherapy were found to have a favorable PFS (P=0.003,P=0.013) and OS (P=0.003, P=0.004) than non-EPI/5-Fu-based treatment, respectively. Conclusion: Our findings confirmed the poor prognosis of high PKM2 expression in breast cancer and revealed the predictive value of PKM2 in therapeutic response to EPI and 5-Fu. Moreover, our results provided the guidance of individual treatment for the patients with poor prognosis prompted by high PKM2 expression.

Key Words: breast cancer  chemosensitivity  PKM2