Wei Zhou1, Lili Lin2, Lian-Yong Jiang3, Jin-Long Wu4, Wei-Chen Xu2, Yang Zhou2, Ma-Jie Wang5, Xiang-Ming Cao6, Hui-Qing Lin7, Jian Yang8, Li-Chun Deng9, Zhi-Hao Zhang10, Jin-Jun Shan11. 1. State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. 2. Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing, China. 3. Department of Thoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 4. Department of Thoracic Surgery, Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China. 5. Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, China. 6. Department of Oncology, The Affiliated Jiangyin Hospital of Nantong University, Wuxi, China. 7. Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China. 8. Department of Cardiothoracic Surgery, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China. yangjian001@njmu.edu.cn. 9. Department of Oncology, The Affiliated Jiangyin Hospital of Nantong University, Wuxi, China. denglc@jyrmyy.com. 10. State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. 1620174425@cpu.edu.cn. 11. Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing, China. jshan@njucm.edu.cn.
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.
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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