Assuming an association between cancer and metabolism, oncogene-directed metabolic reprogramming in cancer has revealed new target strategies. For example, the LKB1-AMPK-mTOR signaling pathway genes are already known to alter the cell metabolism and to play a critical role in the malignant behavior of cancer. Accordingly, based on the assumption that genetic variations in the LKB1-AMPK-mTOR signaling pathway can change the intracellular signal in terms of metabolic reprogramming, the present study analyzed 18 single nucleotide polymorphisms (SNPs) of the STK11, PRKAA1, TSC1/2, and mTOR genes and their impact on the survival of patients with colorectal cancer.
Seven hundred seventy-two patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Eighteen SNPs were selected from an in silico analysis based on previous evidence of association. The SNP genotyping was performed using a SEQUENOM MassARRAY.
Among the 18 polymorphisms, three SNPs (STK11 rs741765, PRKAA1 rs461404, and TSC1 rs13295634) were significantly associated with disease-free survival (DFS) or overall survival (OS). In a multivariate analysis, the GG genotype of STK11, TT genotype of PRKAA1, and TG or GG genotype of TSC1 were identified as independent prognostic factors for a worse DFS (hazard ratio = 1.398, 1.408, and 1.388; p = 0.030, 0.013, and 0.002, respectively) and OS (hazard ratio = 1.431, 1.680, and 1.394; p = 0.038, 0.001, and 0.009, respectively).
The present results suggest that genetic variants of the STK11, PRKAA1, and TSC1 genes could be used as prognostic biomarkers for patients with surgically resected colorectal cancer.
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This work was supported in part by a National Research Foundation of Korea Grant funded by the Korean Government (NRF-2011-0015862) and in part by a Grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111345).
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The authors declare they have no conflict of interest to disclose.
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Lee, S.J., Kang, B.W., Chae, Y.S. et al. Genetic Variations in STK11, PRKAA1, and TSC1 Associated with Prognosis for Patients with Colorectal Cancer. Ann Surg Oncol 21 (Suppl 4), 634–639 (2014). https://doi.org/10.1245/s10434-014-3729-z
- Overall Survival
- Rectal Cancer
- Multiplex Polymerase Chain Reaction
- TSC1 Gene
- Signaling Pathway Gene