Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict platinum-based chemotherapy response of advanced non-small cell lung cancers in a Chinese population.
OBJECTIVE
The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients.


METHODS
Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS).


RESULTS
Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients.


CONCLUSIONS
Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, and Department of Epidemioogy and Biostatistics, MOE Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Jia-Li
JL
Xu
Zhen-Wu
ZW
Wang
Ling-Min
LM
Hu
Zhi-Qiang
ZQ
Yin
Ming-De
MD
Huang
Zhi-Bin
ZB
Hu
Hong-Bing
HB
Shen
Yong-Qian
YQ
Shu
D000230:Adenocarcinoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D016190:Carboplatin; D002945:Cisplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D051059:PTEN Phosphohydrolase; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D043823:Taxoids; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C546842:MTOR protein, human; C494929:PTEN protein, human