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LKB1/AMPK/mTOR 通路中的遗传变异与非小细胞肺癌化疗的临床结局相关。

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

机构信息

Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, South Korea.

出版信息

Thorac Cancer. 2022 Dec;13(23):3322-3330. doi: 10.1111/1759-7714.14688. Epub 2022 Oct 14.

DOI:10.1111/1759-7714.14688
PMID:36239337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9715851/
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.

摘要

本研究旨在探讨 LKB1/AMPK/mTOR 通路中的遗传变异与接受化疗的非小细胞肺癌 (NSCLC) 患者治疗结局之间的关系。共纳入 379 例接受一线紫杉醇-顺铂化疗的 NSCLC 患者。分析了 LKB1/AMPK/mTOR 通路中 19 个单核苷酸变异 (SNVs) 与化疗反应和总生存期 (OS) 的关系。在分析的 SNVs 中，AKT1 rs2494750G>C 和 TSC1 rs2809244C>A 在多变量分析中与化疗后临床结局相关。AKT1 rs2494750G>C 与化疗反应显著相关（调整后的优势比[aOR]：1.92，95%置信区间[CI]：1.02-3.62，p=0.04）。TSC1 rs2809244C>A 与更好的 OS 显著相关（调整后的危险比[aHR]：0.79，95%CI：0.62-0.99，p=0.04）。按肿瘤组织学分层，AKT1 rs2494750G>C 仅在腺癌中与化疗反应显著相关，而 TSC1 rs2809244C>A 也仅在腺癌中与 OS 显著相关。这一结果表明，AKT1 rs2494750G>C 和 TSC1 rs2809244C>A 可能有助于预测 NSCLC 一线紫杉醇-顺铂化疗的临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbf9/9715851/8cdb02412c45/TCA-13-3322-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbf9/9715851/8cdb02412c45/TCA-13-3322-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbf9/9715851/8cdb02412c45/TCA-13-3322-g001.jpg

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