Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities

Area of Science:

• Oncology
• Metabolomics
• Molecular Biology

Background:

• Metabolomic profiling offers insights into tissue physiology but large-scale integrative studies in lung adenocarcinoma (LUAD) are limited.
• Understanding metabolic reprogramming is crucial for advancing cancer research and developing targeted therapies.

Purpose of the Study:

• To conduct a large-scale integrative analysis of metabolomic, transcriptomic, and 16S rRNA sequencing data in LUAD.
• To identify metabolic differences between LUAD subtypes and normal lung tissues.
• To explore potential therapeutic targets based on metabolic findings.

Main Methods:

• Analysis of 262 tissue samples from 165 LUAD patients using multi-omics data (metabolomics, transcriptomics, 16S rRNA sequencing).
• Data integration via a "gene-enzyme-reaction-metabolite" network.
• Evaluation of distinct components within mixed ground-glass opacities (mGGOs) and multiple primary lung cancers (MPLC).
• Utilized cellular and organoid models to validate findings.

Main Results:

• Extensive metabolic reprogramming was observed in LUAD, primarily involving glycerophospholipid metabolism.
• Pure ground-glass opacities (GGOs) and solid nodules (SNs) displayed distinct metabolic profiles, with linoleic acid metabolism differentiating them.
• Components within mGGOs showed metabolic similarity to pure GGOs.
• Phospholipase A2 (PLA2) inhibition or phosphatidylcholine (32:0) treatment reduced LUAD cell invasion and proliferation in vitro.

Conclusions:

• The study reveals significant metabolic heterogeneity within lung adenocarcinoma, impacting glycerophospholipid metabolism.
• Distinct metabolic signatures differentiate LUAD subtypes, suggesting subtype-specific therapeutic vulnerabilities.
• Inhibition of PLA2 and modulation of phosphatidylcholine represent potential therapeutic strategies for LUAD.