GLUT1 rs1385129G>A Raised the Risk and Poor Prognosis of Lung Cancer: A Case-Control Study.
Energy metabolism reprogramming of cancer cells with the abnormal glycolytic capacity represents a novel direction of tumor therapy. Nevertheless, there is a lack of evidence linking genetic variations in glycolysis-related genes to the risk and clinical progression of lung cancer (LC). This study is aimed at clarifying the genetic effect of glycolytic pathway-related genes on the occurrence and development of LC.
In this two-stage case-control study, we enrolled 300 LC patients and 600 healthy controls, as well as 1248 case-control pairs from several hospitals in Guangzhou, to evaluate the association between the genetic variations of glycolysis-related genes (GLUT1 rs1385129G>A, GLUT11 rs6003939A>C, GLUT12 rs1484180G>A and ENO2 rs11064467C>T) and the risk of LC. Follow-up data and the TCGA database were used to evaluate the relationship between GLUT1 rs1385129G>A and GLUT1 expression with the clinical progression of LC.
Only GLUT1 rs1385129G>A was found to be associated with increased risk of LC in this two-stage case-control study (p < 0.05). Further analysis of the expression levels of GLUT1 in GLUT1 rs1385129G>A genotypes showed that they were positively correlated with the number of A alleles (p < 0.01), and the GA genotype had a moderate effect on GLUT1 expression, whereas the AA genotype had a strong effect (GA vs. GG: Cohen's d = 0.768, 95% CI = 0.20-1.02; AA vs. GG: Cohen's d = 1.890, 95% CI = 0.93-3.57). The results were further verified by eQTL analysis based on the GTEx database. The GA and AA genotypes were associated with worse prognosis in LC compared with the GG genotype, as determined by Cox regression (GA + AA vs. GG: HR = 1.37, 95% CI = 1.20-1.57). Furthermore, the survival curve of LC plotted using the GEPIA website showed that the group with high expression of GLUT1 had an increased risk of poor prognosis compared with the low (Log-rank p < 0.01; HR = 1.40). The same result was obtained from the Kaplan-Meier Plotter database (Log-rank p < 0.01; HR = 1.34).
Altogether, GLUT1 rs1385129G>A may increase the risk of LC and contribute to a poor prognosis by upregulating GLUT1 expression.
In this two-stage case-control study, we enrolled 300 LC patients and 600 healthy controls, as well as 1248 case-control pairs from several hospitals in Guangzhou, to evaluate the association between the genetic variations of glycolysis-related genes (GLUT1 rs1385129G>A, GLUT11 rs6003939A>C, GLUT12 rs1484180G>A and ENO2 rs11064467C>T) and the risk of LC. Follow-up data and the TCGA database were used to evaluate the relationship between GLUT1 rs1385129G>A and GLUT1 expression with the clinical progression of LC.
Only GLUT1 rs1385129G>A was found to be associated with increased risk of LC in this two-stage case-control study (p < 0.05). Further analysis of the expression levels of GLUT1 in GLUT1 rs1385129G>A genotypes showed that they were positively correlated with the number of A alleles (p < 0.01), and the GA genotype had a moderate effect on GLUT1 expression, whereas the AA genotype had a strong effect (GA vs. GG: Cohen's d = 0.768, 95% CI = 0.20-1.02; AA vs. GG: Cohen's d = 1.890, 95% CI = 0.93-3.57). The results were further verified by eQTL analysis based on the GTEx database. The GA and AA genotypes were associated with worse prognosis in LC compared with the GG genotype, as determined by Cox regression (GA + AA vs. GG: HR = 1.37, 95% CI = 1.20-1.57). Furthermore, the survival curve of LC plotted using the GEPIA website showed that the group with high expression of GLUT1 had an increased risk of poor prognosis compared with the low (Log-rank p < 0.01; HR = 1.40). The same result was obtained from the Kaplan-Meier Plotter database (Log-rank p < 0.01; HR = 1.34).
Altogether, GLUT1 rs1385129G>A may increase the risk of LC and contribute to a poor prognosis by upregulating GLUT1 expression.
Authors
Li Li, Wang Wang, Chen Chen, Wu Wu, Tang Tang, Huang Huang, Deng Deng, Wang Wang, Qiu Qiu, Yang Yang, Lu Lu
View on Pubmed