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

被引：3

作者：

Ha Choi, Sun ^{[1
,2
]}

Do, Sook Kyung ^{[3
,4
]}

Lee, Shin Yup ^{[1
,2
]}

Choi, Jin Eun ^{[3
,4
]}

Kang, Hyo-Gyoung ^{[3
,4
]}

Hong, Mi Jeong ^{[3
,4
]}

Lee, Jang Hyuck ^{[3
,4
]}

Lee, Won Kee ^{[5
,6
,7
]}

Jeong, Ji Yun ^{[8
]}

Shin, Kyung Min ^{[9
]}

Do, Young Woo ^{[10
]}

Lee, Eung Bae ^{[10
]}

Park, Ji Eun ^{[1
]}

Lee, Yong Hoon ^{[1
]}

Seo, Hyewon ^{[1
]}

Yoo, Seung Soo ^{[1
,2
]}

Lee, Jaehee ^{[1
]}

Cha, Seung Ick ^{[1
]}

Kim, Chang Ho ^{[1
]}

Park, Jae Yong ^{[1
,2
,3
,4
]}

机构：

[1] Kyungpook Natl Univ, Dept Internal Med, Sch Med, Daegu, South Korea

[2] Kyungpook Natl Univ, Lung Canc Ctr, Chilgok Hosp, 807 Hoguk Ro, Daegu 41404, South Korea

[3] Kyungpook Natl Univ, Dept Biochem & Cell Biol, Sch Med, Daegu, South Korea

[4] Kyungpook Natl Univ, Cell & Matrix Res Inst, Sch Med, Daegu, South Korea

[5] Kyungpook Natl Univ, Dept Med Informat, Sch Med, Daegu, South Korea

[6] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Med Res Collaborat Ctr, Daegu, South Korea

[7] Kyungpook Natl Univ, Sch Med, Daegu, South Korea

[8] Kyungpook Natl Univ, Dept Pathol, Sch Med, Daegu, South Korea

[9] Kyungpook Natl Univ, Dept Radiol, Sch Med, Daegu, South Korea

[10] Kyungpook Natl Univ, Thorac Surg, Sch Med, Daegu, South Korea

来源：

THORACIC CANCER | 2022年 / 13卷 / 23期

关键词：

chemotherapy response; LKB1; AMPK; mTOR pathway; lung cancer; survival; variant; MAMMALIAN TARGET; LKB1; SURVIVAL; RESISTANCE; KINASE; MTOR; METABOLISM; ACTIVATION; APOPTOSIS; LESSONS;

D O I：

10.1111/1759-7714.14688

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：3322 / 3330

页数：9

共 38 条

[1] Cancer's sweet tooth: the Janus effect of glucose metabolism in tumorigenesis [J].