Abstract
Introduction
Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates.
Objective
We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics.
Methods
In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics.
Results and conclusion
GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.
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Abbreviations
- GC–MS:
-
Gas chromatography-mass spectrometry
- LC–MS:
-
Liquid chromatography-mass spectrometry
- OPLS-DA:
-
Orthogonal partial least-squared discriminant analysis
- PCA:
-
Principal components analysis
- QC:
-
Quality control
- SPNs:
-
Solitary pulmonary nodules
- VIP:
-
Variable importance in the projection
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Acknowledgements
This work was supported by National Natural Science Foundation of China (Grant No. 81803694, 81904254), Fundamental Research Funds for the Central Universities (Grant No. 2632020ZD07); Natural Science Foundation of Jiangsu Province, China (Grant No. BK20190808); Natural Science Foundation of the Higher Education Institutions of Jiangsu Province, China (Grant No. 19KJB360002); Young Scientists Fund of the National Natural Science Foundation of Nanjing university of Chinese medicine (NZY81904254); Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), No. 87 [2018]; the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions (Grant No. ZYX03KF52). The authors also thank Dr. Raphael N. Alolga from China Pharmaceutical University and American Journal Experts (an editing company) for the editorial services rendered.
Funding
National Natural Science Foundation of China,81803694,81904254,Fundamental Research Funds for the Central Universities,2632020ZD07,Natural Science Foundation of Jiangsu Province,BK20190808,Natural Science Foundation of the Higher Education Institutions of Jiangsu Province,19KJB360002,Young Scientists Fund of the National Natural Science Foundation of Nanjing university of Chinese medicine,NZY81904254,Priority Academic Program Development of Jiangsu Higher Education Institutions,87 [2018],the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions, ZYX03KF52.
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WZ, L-yJ, LL, J-lW, JY, L-cD, Z-hZ and J-jS: conceptualization, Methodology and Writing- Original draft preparation. W-cX, YZ, M-jW, X-mC and H-qL: Data curation and Resources. WZ and J-jS: Investigation and Supervision. WZ and J-jS: Writing- Reviewing and Editing.
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No potential conflict of interest declared.
Ethical approval
The Affiliated Jiangyin Hospital of Southest University Medical College approved this study (2017-036), in accordance with the Declaration of Helsinki, approved use of the patient plasma samples. Patients gave written informed consent before enrolment.
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The mass spectrometry data have been deposited to the Metabolomics Workbench (https://www.metabolomicsworkbench.org/). The study named ST001937. Reviewer account details: Username: jshan12345678. Password: Shan85811329 (http://dev.metabolomicsworkbench.org:22222/data/DRCCMetadata.php?Mode=Study&StudyID=ST001937). Further details and other data that support the findings of this study are available from the corresponding author upon request.
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Wei Zhou, Lili Lin, Lian-yong Jiang and Jin-long Wu are the co-first authors.
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Zhou, W., Lin, L., Jiang, Ly. et al. Comprehensive plasma metabolomics and lipidomics of benign and malignant solitary pulmonary nodules. Metabolomics 18, 71 (2022). https://doi.org/10.1007/s11306-022-01929-0
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DOI: https://doi.org/10.1007/s11306-022-01929-0