TY - JOUR
T1 - Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities
AU - Li, Bowen
AU - Wang, Daoyun
AU - Wang, Yadong
AU - Huang, Zhicheng
AU - Liu, Qianshu
AU - Zheng, Zhibo
AU - Gao, Chao
AU - Lin, Yuxiao
AU - Liu, Lei
AU - Wang, Zhina
AU - Wei, Zewen
AU - Li, Shanqing
AU - Zhang, Nan
AU - Liang, Naixin
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12
Y1 - 2026/12
N2 - Metabolomic profiling provides real-time insights into tissue physiology and upstream molecular events. Despite its potential in cancer research, large-scale integrative studies in lung adenocarcinoma (LUAD) remain scarce. We analyzed 262 tissue samples from 165 LUAD patients using metabolomic, transcriptomic, and 16S rRNA sequencing, integrating data through a “gene-enzyme-reaction-metabolite” network. Distinct components of mixed ground-glass opacities (mGGOs) and lesions from multiple primary lung cancers (MPLC) were also evaluated separately. Our results revealed extensive metabolic reprogramming in LUAD, predominantly affecting glycerophospholipid metabolism. Pure ground-glass opacities (GGOs) and solid nodules (SNs) exhibited markedly distinct metabolic profiles, with linoleic acid metabolism as a key differentiator. In contrast, components within mGGOs were metabolically similar, resembling pure GGOs. Cellular and organoid models demonstrated that phospholipase A2 (PLA2) inhibition or phosphatidylcholine (32:0) treatment significantly attenuated invasion and proliferation of LUAD cells. These findings provide a metabolic basis for subtype-specific LUAD biology and potential therapeutic strategies.
AB - Metabolomic profiling provides real-time insights into tissue physiology and upstream molecular events. Despite its potential in cancer research, large-scale integrative studies in lung adenocarcinoma (LUAD) remain scarce. We analyzed 262 tissue samples from 165 LUAD patients using metabolomic, transcriptomic, and 16S rRNA sequencing, integrating data through a “gene-enzyme-reaction-metabolite” network. Distinct components of mixed ground-glass opacities (mGGOs) and lesions from multiple primary lung cancers (MPLC) were also evaluated separately. Our results revealed extensive metabolic reprogramming in LUAD, predominantly affecting glycerophospholipid metabolism. Pure ground-glass opacities (GGOs) and solid nodules (SNs) exhibited markedly distinct metabolic profiles, with linoleic acid metabolism as a key differentiator. In contrast, components within mGGOs were metabolically similar, resembling pure GGOs. Cellular and organoid models demonstrated that phospholipase A2 (PLA2) inhibition or phosphatidylcholine (32:0) treatment significantly attenuated invasion and proliferation of LUAD cells. These findings provide a metabolic basis for subtype-specific LUAD biology and potential therapeutic strategies.
UR - https://www.scopus.com/pages/publications/105037763077
U2 - 10.1038/s41698-026-01378-1
DO - 10.1038/s41698-026-01378-1
M3 - Article
AN - SCOPUS:105037763077
SN - 2397-768X
VL - 10
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 174
ER -