染色体异常是与癌症预后、化疗、免疫治疗和药物耐药相关的基因组特征。本研究旨在调查染色体拷贝数变异（CNVs）对EGFR突变非小细胞肺癌（NSCLC）患者酪氨酸激酶抑制剂（TKIs）疗效的影响，以及其对EGFR野生型患者无进展生存期（PFS）和总生存期（OS）的预后意义。本研究纳入了110例晚期NSCLC患者，分为EGFR突变组和野生型组。利用下一代测序（NGS）技术，我们评估了与肺癌通路相关的24个基因和染色体CNVs在患者组织样本中的表达情况。在EGFR突变组中，具有Chr 1p13.3-p13.1增益的患者显示出较差的TKI疗效、较高的复发率和较短的PFS（P = 0.002）。相反，在EGFR突变患者中，具有14q31.1-q31.3增益的患者显示出较好的TKI疗效和相对较长的PFS（P = 0.005）。在EGFR野生型患者中，7q31.1-q31.31 CNV的存在成为影响PFS和OS的独立因素（P = 0.013，P = 0.004）。值得注意的是，具有7q31.1-q31.31增益的患者显示出较长的PFS和OS。此外，9q21.31-q22.2和11p11.11-q12.1区域CNVs对EGFR野生型患者的OS具有独立的预后意义（P = 0.001）。在这些区域的增益预示着较长的OS，而缺失则预测了较差的预后。我们的结果表明，染色体拷贝数变异是预测NSCLC患者对EGFR靶向治疗反应和预后的实际指标。 © 2023 He et al.

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.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.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.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.© 2023 He et al.