The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non-Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy.
The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR]=1.39; 95% confidence interval [CI]=1.16-1.66; P=.0003) and OS (adjusted HR=1.41; 95% CI=1.11-1.80; P=.005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR=0.86; 95% CI=0.56-1.33; P=.505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China. Electronic address: 14111230007@fudan.edu.cn.
Ming
M
Jia
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China. Electronic address: 14111230023@fudan.edu.cn.
Yuan
Y
Xu
Department of Oncology, Xinhua Hospital affiliated to Shanghai Jiaotong University, School of Medicine, No. 1665, Kong Jiang Road, Shanghai, 200092, China. Electronic address: anniezhu_79@163.com.
Meiling
M
Zhu
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China. Electronic address: wangmengyun1120@163.com.
Mengyun
M
Wang
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai, 200032, China. Electronic address: menghongs@163.com.
Menghong
M
Sun
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, 200032, China. Electronic address: qianji2012@126.com.
Ji
J
Qian
Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China; Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai, 200032, China. Electronic address: changjianhua@163.com.
Jianhua
J
Chang
Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Xuhui, Shanghai, 200032, China; Duke Cancer Institute, Duke University Medical Center, and Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. Electronic address: weiqingyi@yahoo.com.
Qingyi
Q
Wei