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

Sun Ha Choi, Sook Kyung Do, Shin Yup Lee, Jin Eun Choi, Hyo Gyoung Kang, Mi Jeong Hong, Jang Hyuck Lee, Won Kee Lee, Ji Yun Jeong, Kyung Min Shin, Young Woo Do, Eung Bae Lee, Ji Eun Park, Yong Hoon Lee, Hyewon Seo, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Jae Yong Park

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)3322-3330
Number of pages9
JournalThoracic Cancer
Volume13
Issue number23
DOIs
StatePublished - Dec 2022

Keywords

  • chemotherapy response
  • LKB1/AMPK/mTOR pathway
  • lung cancer
  • survival
  • variant

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