Plasma metabolomic analysis in Thai EGFR-mutated non-small cell lung cancer patients

TL;DR

This study identifies unique plasma metabolite patterns in Thai lung cancer patients with EGFR mutations, which could help in diagnosis and monitoring treatment response.

Contribution

The study provides precise metabolite identification and links plasma metabolites to EGFR mutation status and TKI resistance in NSCLC patients.

Findings

NSCLC patients had elevated glycine and reduced tryptophan and inositol compared to healthy controls.

Metabolic shifts in amino acids and organic acids distinguished EGFR-mutated from wild-type NSCLC.

Altered levels of tryptophan, valine, and oxalic acid were linked to resistance to EGFR tyrosine kinase inhibitors.

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, underscoring the urgent need for non-invasive approaches to improve diagnosis, patient stratification, and therapeutic monitoring. Metabolic reprogramming driven by oncogenic alterations—particularly Epidermal Growth Factor Receptor (EGFR) mutations in non-small cell lung cancer (NSCLC)—creates distinctive plasma signatures with clinical relevance. In this study, plasma metabolomic profiling revealed that amino acid and sugar metabolism exhibited the strongest discriminatory patterns. NSCLC patients consistently showed elevated glycine and reduced tryptophan and inositol compared with healthy controls. Distinct amino acid and organic acid shifts further differentiated EGFR-mutated from wild-type NSCLC, while alterations in tryptophan, valine, and oxalic acid characterized patients with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). These findings underscore biologically relevant metabolic alterations associated with EGFR mutation and TKI resistance, supporting the potential of plasma metabolite profiles as minimally invasive indicators for molecular classification and treatment response in NSCLC.

•Profiles metabolic alterations in NSCLC by EGFR mutation and TKI resistance.•Links plasma metabolites with clinical features and survival.•Provides absolute quantification and precise metabolite identification, enhancing reproducibility.•Reveals metabolic changes in patients with acquired EGFR TKI resistance.

Profiles metabolic alterations in NSCLC by EGFR mutation and TKI resistance.

Links plasma metabolites with clinical features and survival.

Provides absolute quantification and precise metabolite identification, enhancing reproducibility.

Reveals metabolic changes in patients with acquired EGFR TKI resistance.

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