非小细胞肺癌（NSCLC）是最常见的肺肿瘤类型。尽管进行了手术切除，但复发率很高，占所有病例的30-55%。基于定制基因组的下一代测序 (NGS) 和循环肿瘤细胞 (CTC) 分析可以帮助识别异质性、对高风险患者进行分层并指导治疗决策。在这项涉及小型前瞻性队列的描述性研究中，我们重点关注 CTC 的表型特征，特别是 EZH2 表达（Polycomb 抑制复合物 2 的成员），以及使用定制基因组和组织的突变谱。在可切除的 NSCLC 患者中，在手术切除前 (CTC1) 和手术后 1 个月 (CTC2) 评估了 EZH2 在 CTC 上的分离和特征。使用定制的 50 基因组对一部分患者的组织样本进行靶向 NGS。招募了 76 名可切除 NSCLC 患者。该队列中最常见的突变基因包括 TP53、FLT1、MUC5AC、EGFR 和 NLRP3。具有相互排斥突变的基因对是TP53-RIN3，具有共存突变的基因对是CD163-TLR4、FGF10-FOXP2、ADAMTSL3-FLT1、ADAMTSL3-MUC5AC和MUC5AC-NLRP3。 CTC1 和 CTC2 两个时间点之间的 CTC 显着下降 (p<0.0001)，并且 EZH2 高表达的 CTC 患者的死亡风险增加 87% (p=0.018)。整合肿瘤的分子分析和 CTC 表征可以提供有价值的见解深入了解肿瘤异质性并改善可切除 NSCLC 的患者分层。版权所有 © 2024 SEPAR。由 Elsevier España 出版，S.L.U.版权所有。

Non-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30-55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions. In this descriptive study involving a small prospective cohort, we focus on the phenotypic characterization of CTCs, particularly concerning EZH2 expression (a member of the Polycomb Repression Complex 2), as well as on the mutation profiles of the tissue using a customized gene panel and their association with poor outcomes in NSCLC.Isolation and characterization of EZH2 on CTCs were evaluated before surgical resection (CTC1) and one month after surgery (CTC2) in resectable NSCLC patients. Targeted NGS was performed using a customized 50-gene panel on tissue samples from a subset of patients.76 patients with resectable NSCLC were recruited. The top mutated genes in the cohort included TP53, FLT1, MUC5AC, EGFR, and NLRP3. Pair of genes that had mutually exclusive mutations was TP53-RIN3, and pairs of genes with co-occurring mutations were CD163-TLR4, FGF10-FOXP2, ADAMTSL3-FLT1, ADAMTSL3-MUC5AC and MUC5AC-NLRP3. CTCs decreased significantly between the two time points CTC1 and CTC2 (p<0.0001), and CTCs+ patients with high EZH2 expression had an 87% increased risk of death (p=0.018).Integrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.