LAUSR

AMP‐activated protein kinase (AMPK) is a key sensor of energy homeostasis and regulates cell metabolism, proliferation and chemotherapy/radiotherapy sensitivities. This study aimed to explore the relationship between the AMPK pathway‐related single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with metastatic colorectal cancer (mCRC). We analyzed a total of 884 patients with mCRC enrolled in three randomized clinical trials (TRIBE, MAVERICC and FIRE‐3: where patients were treated with FOLFIRI, mFOLFOX6 or FOLFOXIRI combined with bevacizumab or cetuximab as the first‐line chemotherapy). The association between AMPK pathway‐related SNPs and clinical outcomes was analyzed across the six treatment cohorts, using a meta‐analysis approach. Our meta‐analysis showed that AMPK pathway had significant associations with progression‐free survival (PFS; p < 0.001) and overall survival (OS; p < 0.001), but not with tumor response (TR; p = 0.220): PRKAA1 rs13361707 was significantly associated with favorable PFS (log HR = −0.219, SE = 0.073, p = 0.003), as well as PRKAA1 rs10074991 (log HR = −0.215, SE = 0.073, p = 0.003), and there were suggestive associations of PRKAG1 rs1138908 with unfavorable OS (log HR = 0.170, SE = 0.083, p = 0.041), and of UBE2O rs3803739 with unfavorable PFS (log HR = 0.137, SE = 0.068, p = 0.042) and OS (log HR = 0.210, SE = 0.077, p = 0.006), although these results were not significant after false discovery rate adjustment. AMPK pathway‐related SNPs may be predictors for chemotherapy in mCRC. Upon validation, our findings would provide novel insight for selecting treatment strategies.