2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06F.01 Proteomic Profiling Reveals Distinct Biological Characteristics of EGFR L858R Mutation and a Prognostic Model in Lung Adenocarcinoma

P3.06F.01 Proteomic Profiling Reveals Distinct Biological Characteristics of EGFR L858R Mutation and a Prognostic Model in Lung Adenocarcinoma

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The study detailed in the document investigates the biological and molecular characteristics of different subtypes of EGFR (epidermal growth factor receptor) mutations in lung adenocarcinoma, particularly focusing on the L858R subtype, which is linked to more aggressive behavior and poorer prognosis compared to the 19DEL subtype and wild-type EGFR. Researchers used isogenic NCI-H520 cell line models with EGFR mutations (WT, 19DEL, and L858R) developed through stable lentiviral transfection.<br /><br />Proteomic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS) to explore the proteomic differences among these mutations, revealing distinct biological characteristics for the L858R mutation. Notably, 11 proteins showed significantly higher expression in L858R compared to 19DEL and WT. In contrast, 9 proteins showed lower expression levels in the L858R mutation.<br /><br />Further analyses, including gene set enrichment and integrative bioinformatics approaches, highlighted pathways commonly enriched in 19DEL and L858R—such as ribosome and antigen processing and presentation—and uniquely enriched metabolic pathways for L858R. The study identified 28 differentially expressed genes between EGFR mutants and wild-type samples.<br /><br />A prognostic model based on 4 genes was constructed to predict disease-free survival (DFS) in patients with EGFR-mutated lung adenocarcinoma. Higher expressions of BAG4, PLGRKT, and PRIM1 were associated with worse DFS, while higher MOCS2 expression correlated with improved DFS. Multivariate analysis confirmed PRIM1 as an independent prognostic factor for DFS.<br /><br />This comprehensive proteomic and bioinformatic analysis not only elucidates the distinctive proteomic landscape of the L858R mutation but also offers valuable insights for future therapeutic strategies and prognosis in lung adenocarcinoma patients. PRIM1 is identified as a potential prognostic biomarker, warranting further investigation.

Asset Subtitle

Jie Huang

Meta Tag

Speaker Jie Huang

Topic Pathology & Biomarkers

Keywords

EGFR mutations

lung adenocarcinoma

L858R subtype

proteomic profiling

liquid chromatography-mass spectrometry

differentially expressed genes

prognostic model

disease-free survival

PRIM1 biomarker

therapeutic strategies