Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Platinum-based Chemotherapy Response of Advanced Non-small Cell Lung Cancers in a Chinese Population

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin.In the current study, we determined whether common genetic variations in this pathway are associated withplatinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC)patients.
Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway weregenotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival(PFS) and overall survival (OS).
Results: Logistic regression analysis revealed an association between AKT1rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of diseaseprogression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjustedodds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratifiedanalyses). However, log-rank test and cox regression detected no association between these polymorphisms inthe PI3K pathway genes and survival in advanced NSCLC patients.
Conclusions: Our findings suggest thatgenetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy responsein advanced NSCLC patients in a Chinese population.