ArticleJournal of gastrointestinal oncology2026
Intratumoral PKM2 expression predicts benefit from adjuvant FOLFOX in stage II-III colorectal cancer.
Article in Journal of gastrointestinal oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Clinicopathological risk factors in non-metastatic colorectal cancer provide prognostic information but have limited ability to identify patients who benefit from specific adjuvant chemotherapy regimens. Pyruvate kinase M2 (PKM2), a key regulator of aerobic glycolysis and tumor proliferation, has been linked to chemotherapy sensitivity in a regimen-dependent manner. This study evaluated intratumoral PKM2 expression as a predictive biomarker for the effectiveness of oxaliplatin-based adjuvant chemotherapy in stage II/III colorectal cancer. Methods: In this retrospective cohort study, consecutive patients with stage II/III colorectal cancer who underwent curative-intent surgery between 2008 and 2012 were analyzed. PKM2 expression in primary tumors was assessed by immunohistochemistry and dichotomized as positive or negative. Patients were categorized into no adjuvant chemotherapy (NoAC), fluoropyrimidine monotherapy (FP), and oxaliplatin-based combination chemotherapy (FOLFOX) groups. Weighted Cox proportional hazards models using energy-based covariate balancing weights were used to estimate average treatment effects. Treatment-by-marker interaction tests were performed to assess predictive value. Results: Among 193 patients (mean age 66.2±10.4 years; 110 men), 98 (51%) were PKM2-positive. Ninety-three (48%) and 52 (27%) patients received 5-fluorouracil (5-FU) and FOLFOX, respectively. In PKM2-positive patients, FOLFOX was associated with improved overall survival compared with NoAC [hazard ratio (HR) =0.10; 95% confidence interval (CI): 0.02-0.38], whereas no clear benefit was observed in PKM2-negative patients (HR =0.77; 95% CI: 0.33-1.79) (interaction P=0.01). When compared with FP, FOLFOX conferred greater survival benefit in PKM2-positive patients (HR =0.25; 95% CI: 0.07-0.96), while outcomes tended to be poorer in PKM2-negative patients (HR =2.39; 95% CI: 0.80-7.18) (interaction P=0.01). The treatment-by-marker interactions for FOLFOX Conclusions: Intratumoral PKM2 expression may be a regimen-specific predictive biomarker for survival benefit from adjuvant FOLFOX in stage II/III colorectal cancer. Prospective validation is warranted before clinical implementation.
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