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Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities
  • Published: 17 March 2026

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

  • Bowen Li1 na1,
  • Daoyun Wang1 na1,
  • Yadong Wang1,
  • Zhicheng Huang1,
  • Qianshu Liu1,
  • Zhibo Zheng1,
  • Chao Gao1,
  • Yuxiao Lin1,
  • Lei Liu1,
  • Zhina Wang2,
  • Zewen Wei3,
  • Shanqing Li1,
  • Nan Zhang2 &
  • …
  • Naixin Liang1 

, Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

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.

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Data availability

The metabolomics data have been deposited in the MetaboLights repository with the study identifier MTBLS13565 (https://www.ebi.ac.uk/metabolights/MTBLS13565)79. The transcriptome data and 16S rRNA sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) with the dataset identifier PRJNA1393044 (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA1393044).

Code availability

All codes are open source and available at https://github.com/NaixinLiang/LUAD_GGO_vs._SN-Metabolomics/tree/R-files.

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Acknowledgements

We gratefully acknowledge the Clinical Biobank (ISO 20387), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, for the proper storage and management of valuable specimens. Finally, we thank MajorBio Technology Co., Ltd. for providing the technical support for metabolomic and transcriptomic sequencing. This research was supported by grants from Peking Union Medical College Hospital Talent Cultivation Program (Category B) (No. UGG06265), CAMS Innovation Fund for Medical Sciences (No. 2023-I2M-C&T-B-0192), National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-B-011), National Key Research and Development Program of China (No.2024YFB4708805) and Beijing Natural Science Foundation (No. L258029). The funders had no role in the study design, data collection, analysis, or interpretation, nor in the writing of the manuscript or the decision to submit it for publication.

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  1. These authors contributed equally: Bowen Li, Daoyun Wang.

Authors and Affiliations

  1. Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Bowen Li, Daoyun Wang, Yadong Wang, Zhicheng Huang, Qianshu Liu, Zhibo Zheng, Chao Gao, Yuxiao Lin, Lei Liu, Shanqing Li & Naixin Liang

  2. Department of Pulmonary and Critical Care Medicine 2, Emergency General Hospital, Beijing, China

    Zhina Wang & Nan Zhang

  3. Department of Biomedical Engineering, School of Medical Technology, Beijing Institute of Technology, Beijing, China

    Zewen Wei

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Contributions

B.L. and D.W. were responsible for manuscript writing, data visualization, and experimental procedures. Y.W., Z.H., and Q.L. provided and analyzed the clinical data. Z.Z., C.G., Y.L., and L.L. contributed clinical resources and provided input on imaging interpretation. Z.W. participated in a multidisciplinary evaluation. Z.W. offered methodological guidance for experimental procedures. S.L., N.Z., and N.L. jointly supervised the project, critically revised the manuscript, and approved the final version for publication. N.L. and S.L. also provided funding support. All authors reviewed the manuscript and approved the final version for publication.

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Li, B., Wang, D., Wang, Y. et al. Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01378-1

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  • Received: 13 August 2025

  • Accepted: 07 March 2026

  • Published: 17 March 2026

  • DOI: https://doi.org/10.1038/s41698-026-01378-1

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