Genetic variants in LKB1/AMPK/mTOR pathway are associated with clinical outcomes of chemotherapy in non-small cell lung cancer

Abstract

This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first-line paclitaxel-cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02-3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62-0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.

Keywords: LKB1/AMPK/mTOR pathway; chemotherapy response; lung cancer; survival; variant.