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Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer

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 E...

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Autores principales: He, Haiyan, Ma, Hang, Chen, Zhuo, Chen, Jingliang, Wu, Dandan, Lv, Xuedong, Zhu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10505391/
https://www.ncbi.nlm.nih.gov/pubmed/37724294
http://dx.doi.org/10.2147/PGPM.S418320
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author He, Haiyan
Ma, Hang
Chen, Zhuo
Chen, Jingliang
Wu, Dandan
Lv, Xuedong
Zhu, Jie
author_facet He, Haiyan
Ma, Hang
Chen, Zhuo
Chen, Jingliang
Wu, Dandan
Lv, Xuedong
Zhu, Jie
author_sort He, Haiyan
collection PubMed
description 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.
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spelling pubmed-105053912023-09-18 Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer He, Haiyan Ma, Hang Chen, Zhuo Chen, Jingliang Wu, Dandan Lv, Xuedong Zhu, Jie Pharmgenomics Pers Med Original Research 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. Dove 2023-09-13 /pmc/articles/PMC10505391/ /pubmed/37724294 http://dx.doi.org/10.2147/PGPM.S418320 Text en © 2023 He et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
He, Haiyan
Ma, Hang
Chen, Zhuo
Chen, Jingliang
Wu, Dandan
Lv, Xuedong
Zhu, Jie
Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title_full Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title_fullStr Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title_full_unstemmed Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title_short Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer
title_sort chromosomal copy number variation predicts egfr-tki response and prognosis for patients with non-small cell lung cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10505391/
https://www.ncbi.nlm.nih.gov/pubmed/37724294
http://dx.doi.org/10.2147/PGPM.S418320
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