Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

Abel Garcia-Diaz; María José Moyano-Rodríguez; María Del Carmen Garrido-Navas; Diego de Miguel-Perez; Jose Expósito-Hernández; Bernardino Alcázar-Navarrete; Francisco Ortuño; David Landeira; Pedro J Romero; Adrian Garcia-Moreno; Jose A Lorente; Javier Lopez-Hidalgo; Clara Bayarri-Lara; Maria Jose Serrano

doi:10.1016/j.arbres.2024.08.006

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

Arch Bronconeumol. 2024 Oct 4:S0300-2896(24)00360-0. doi: 10.1016/j.arbres.2024.08.006. Online ahead of print.

[Article in English, Spanish]

Authors

Affiliations

¹ GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, 18016 Granada, Spain.
² Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain.
³ Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Medical System & Icahn School of Medicine, Mount Sinai, New York, NY, USA.
⁴ IBS Granada, Instituto de Investigacion Biosanitaria de Granada, 18012 Granada, Spain; Comprehensive Oncology Division, Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain.
⁵ Department of Pneumology Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain.
⁶ Department of Computer Engineering, Automation and Robotics, University of Granada, Granada 18071, Spain.
⁷ Department of Medicine School of Medicine, University of Granada, 18016 Granada, Spain.
⁸ IBS Granada, Instituto de Investigacion Biosanitaria de Granada, 18012 Granada, Spain; Molecular Pathology Lab, Pathology Service, Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain.
⁹ Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: [email protected].
¹⁰ GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, 18016 Granada, Spain; IBS Granada, Instituto de Investigacion Biosanitaria de Granada, 18012 Granada, Spain; Molecular Pathology Lab, Pathology Service, Virgen de las Nieves University Hospital, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: [email protected].

PMID: 39414465
DOI: 10.1016/j.arbres.2024.08.006

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: Integrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.

Keywords: CTCs; EZH2; Liquid biopsy; MRD; NGS; NSCLC.