TY - JOUR
T1 - Genetic Variations in STK11, PRKAA1, and TSC1 Associated with Prognosis for Patients with Colorectal Cancer
AU - Lee, Soo Jung
AU - Kang, Byung Woog
AU - Chae, Yee Soo
AU - Kim, Hye Jin
AU - Park, Su Yeon
AU - Park, Jun Seok
AU - Choi, Gyu Seog
AU - Jeon, Hyo Sung
AU - Lee, Won Kee
AU - Kim, Jong Gwang
N1 - Publisher Copyright:
© 2014, Society of Surgical Oncology.
PY - 2014
Y1 - 2014
N2 - Background: 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.Methods: 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.Results: 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).Conclusions: 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.
AB - Background: 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.Methods: 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.Results: 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).Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=84939894449&partnerID=8YFLogxK
U2 - 10.1245/s10434-014-3729-z
DO - 10.1245/s10434-014-3729-z
M3 - Article
C2 - 24770722
AN - SCOPUS:84939894449
SN - 1068-9265
VL - 21
SP - 634
EP - 639
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 4
ER -
