Polymorphisms in epidermal growth factor receptor (EGFR) and AKT1 as possible predictors of clinical outcome in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors.

Abstract

This study aimed to investigate the association of epidermal growth factor receptor (EGFR) gene polymorphism and AKT1 polymorphism with the clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The clinical outcome and the survival of NSCLC of 230 patients after treatment with EGFR-TKIs were measured. The rs712829, rs1468727 of the EGFR gene and rs1130214 of the AKT1 gene from peripheral blood cell were detected by a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was analyzed. The response rates and the disease control rate of patients with genotype GG, GT, and TT in EGFR rs712829 were statistically very significant difference(19.7 vs 36.1 vs 50.0 %, P = 0.016 and 57.7 vs 77.8 vs 83.3 %, P = 0.026, respectively). Better disease control was also achieved in patients with the GG genotype of AKT1 rs1130214 than those with the GT and TT genotypes (65.6 vs. 48.7 %, P = 0.043). Patients carrying the EGFR rs712829 TT genotype had significantly longer PFS and OS than those with the GT or GG genotypes (9.0 vs. 7.0 vs. 5.0 months, P = 0.001 and 13.1 vs. 14.6 vs. 18.8 months, P = 0.008, respectively). In addition, patients carrying the AKT1 rs1130214 GG genotype also had significantly longer PFS than those with the GT and TT genotypes (5.5 vs. 4.5 months, P = 0.008). EGFR rs712829 polymorphism and AKT1 rs1130214 could influence the response to EGFR-TKIs therapy in patients with advanced NSCLC.

• Authors: Xiaoqing Zhang, Junwei Fan, Yuping Li, Shengtao Lin, Ping Shu, Jian Ni, Shengying Qin, Zhemin Zhang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 1 Pg. 1061-9 (Jan 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26269114 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• ErbB Receptors
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality, pathology)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Genotype
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Mutation
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Prognosis
• Proportional Hazards Models
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-akt (genetics)
• Treatment Outcome
• Young Adult