Abstract
Purpose
Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients.
Methods
A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients’ tissue samples.
Results
Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS (P = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS (P = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS (P = 0.013, P = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions (P = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes.
Conclusion
Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.
Abbreviation
EGFR, Epidermal Growth Factor Receptor; TKI, Tyrosine Kinase Inhibitor; PFS, Progression-Free Survival; OS, Overall Survival; NGS, Next Generation Sequencing; NSCLC, Non-Small Cell Lung Cancer; CNV, Copy Number Variation; UCAD, Ultrasensitive Chromosomal Aneuploidy Detector; TMB, Tumor Mutant Burden.
Data Sharing Statement
All data that can prove the conclusion of this article are included in the article.
Ethical Approval
The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The trial was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The protocol was approved by the institutional Review Board of Nantong First People’s Hospital (NO.2017KY198).
Consent to Participate
All included patients got approved information materials and have provided a written consent.
Consent for Publication
All authors have agreed to publish the current document.
Acknowledgments
Haiyan He and Hang Ma are co-first authors for this study. The authors acknowledge the Suzhou Biomedical Research & Development Center to provide excellent NGS detection technology.
Disclosure
The authors report no conflicts of interest in this work.