Alterations in EGFR and related genes following neo-adjuvant chemotherapy in Chinese patients with non-small cell lung cancer
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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.
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Chemotherapy may selectively kill and inhibit mutant clones within the tumor, whereas wild type clones may proliferate, altering the relative proportion of EGFR-mutated/EGFR-wild type cells within the tumor mass.
“Chemotherapy may selectively kill and inhibit mutant clones within the tumor, whereas wild type clones may proliferate, altering the relative proportion of EGFR-mutated/EGFR-wild type cells within the tumor mass.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [46]
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- Authors
- Wang, S., An, T., Duan, J., Zhang, L., Wu, M., Zhou, Q., Chen, J., Zhuo, M., Yang, L., Wang, Y., Bai, H., & Wang, J.
- Affiliations
- Peking University Cancer Hospital (CN)
- Tianjin Medical University General Hospital (CN)
- Corresponding author
- Bai, Hua
- Wang, Jie
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-08
- Volume
- 8
- Issue
- 3
- Pages
- e51021
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3592850
- OpenAlex
- W2019582655
- Cited by
- 7
- References
- 36
- Citations by year
- 2017: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 1
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Chinese Center for Disease Control and Prevention
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- non-small cell lung cancer, neoadjuvant chemotherapy, EGFR mutation, EGFR tyrosine kinase inhibitors, EGFR signaling, KRAS mutation, MET amplification, T790M mutation, Chinese patients
- MeSH terms
- Adult, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Proto-Oncogene Proteins, Retrospective Studies, Proto-Oncogene Proteins p21(ras), ras Proteins, Proto-Oncogene Proteins c-met, Neoadjuvant Therapy, Protein Kinase Inhibitors, Mutation Rate, ErbB Receptors
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