|Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer|
|Wang, Shuhang1; An, Tongtong1; Duan, Jianchun1; Zhang, Lijian2; Wu, Meina1; Zhou, Qinghua3; Chen, Jinfeng2; Zhuo, Minglei1; Yang, Lu1; Wang, Yuyan1; Bai, Hua1; Wang, Jie1|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||FACTOR RECEPTOR MUTATIONS ; MET AMPLIFICATION ; GEFITINIB ; ERLOTINIB ; TUMORS ; SENSITIVITY ; RESISTANCE|
Introduction: Genetic aberrancies within epidermal growth factor receptor (EGFR) pathway are associated with therapeutic outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on EGFR-related genes alterations has not been defined in NSCLC. Our study aims to investigate the impact of neoadjuvant chemotherapy (Neoadj-Chemo) on EGFR activating mutations and associated EGFR-TKIs resistance-related genes.
Patients and Methods: Matched tumor samples were obtained retrospectively from 66 NSCLC patients (stages IIb-IIIb) corresponding to pre-and post-Neoadj-Chemo. EGFR mutations were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by Amplification Refractory Mutation System technology (ARMS), KRAS mutations, T790M mutation and c-MET amplification were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), ARMS, and real-time PCR, respectively.
Results: Before Neoadj-Chemo, EGFR mutations were identified in 33.3% (22/66) of NSCLC patients. Only 18.2% (12/66) of patients carried EGFR mutations after Neoadj-Chemo (p = 0.013). The median peak value of EGFR 19 exon mutations decreased non-significantly after Neoadj-Chemo. KRAS mutation rate decreased from 4.6% (3/66) to 3.0% (2/66) with Neoadj-Chemo. Although the overall percentage of patients exhibiting c-MET amplifications (6.1% [4/66]) did not change with Neoadj-Chemo, two patients transitioned from negative to positive c-MET amplification, and two patients reversed these changes post-Neoadj-Chemo. T790M mutations were absent from all samples.
Conclusion: Neoadjuvant chemotherapy tends to decrease the mutation frequency of EGFR mutation and downstream genes, which suggests that real-time samples analysis for genetic aberrancies within EGFR pathways have important value to delineate specific patient populations and facilitate individualized treatment.
|项目编号||81025012 ; 81172235 ; 2007-1023 ; 2011-2-22 ; Z090507017709015 ; 81101726|
|资助机构||National Natural Sciences Foundation Distinguished Young Scholars ; National Natural Sciences Foundation General Program ; Capital Development Foundation ; Beijing Health Systems Academic Leader ; Science and Technology Project of Beijing ; National Natural Sciences Foundation China Youth Science Foundation|
|作者单位||1.Peking Univ, Sch Oncol, Dept Thorac Med Oncol,Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China|
2.Peking Univ, Sch Oncol, Dept Thorac Surg,Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China
3.Tianjin Med Univ Gen Hosp, Dept Thorac Surg, Tianjin, Peoples R China
|Wang, Shuhang,An, Tongtong,Duan, Jianchun,et al. Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer[J]. PLOS ONE,2013,8(3).|
|APA||Wang, Shuhang.,An, Tongtong.,Duan, Jianchun.,Zhang, Lijian.,Wu, Meina.,...&Wang, Jie.(2013).Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer.PLOS ONE,8(3).|
|MLA||Wang, Shuhang,et al."Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer".PLOS ONE 8.3(2013).|