2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.05 A Novel DNA Repair-Gene Model to Predict Responses to Immunotherapy and Prognosis in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

P1.03D.05 A Novel DNA Repair-Gene Model to Predict Responses to Immunotherapy and Prognosis in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Back to course

Pdf Summary

This study explores a novel DNA-repair gene model to predict the response to immunotherapy and prognosis in patients with epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC). EGFRm NSCLC is characterized by a unique "cold" immune profile, and DNA-damage repair (DDR) genes are closely linked to tumorigenesis and treatment effectiveness.<br /><br />The researchers identified two subtypes of EGFRm NSCLC: DDR-activated and DDR-suppressed. The DDR-activated subtype demonstrates more aggressive clinical behavior, poorer prognosis, but a better response to immunotherapy compared to the DDR-suppressed subtype. They developed a prognostic model including four DDR genes: CAPS, FAM83A, IGLV8-61, and SLC7A5. This model provides a risk score that serves as an independent prognostic indicator, distinguishing high-risk from low-risk patients, with the latter exhibiting better clinical outcomes and enhanced effectiveness from immunotherapy.<br /><br />The study utilized 101 EGFRm NSCLC samples from The Cancer Genome Atlas and 246 samples from an external GSE dataset. Cluster analysis identified DDR subtypes, and LASSO regression helped develop the predictive model. Bioinformatics analyses revealed different clinicopathological characteristics and immune profiles in high- and low-risk subgroups, focusing on T-cell inflammation and Tumor Immune Dysfunction and Exclusion (TIDE) scores.<br /><br />Furthermore, the study highlights BI.2536, a polo-like kinase 1 inhibitor, as a targeted therapy for high-risk EGFRm NSCLC patients. This comprehensive analysis underscores the importance of DDR gene diversity in EGFRm NSCLC, offering a predictive tool for tailoring immunotherapy treatments to improve patient outcomes. <br /><br />In conclusion, the study provides a new framework for assessing personalized treatment and prognosis in EGFRm NSCLC that could potentially enhance the identification of candidates for immunotherapy.

Asset Subtitle

Fen Wang

Meta Tag

Speaker Fen Wang

Topic Tumor Biology – Translational Biology

Keywords

DNA-repair gene model

immunotherapy response

EGFR mutant NSCLC

cold immune profile

DNA-damage repair genes

prognostic model

DDR subtypes

BI.2536 inhibitor

personalized treatment

tumorigenesis