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Liu B, Shi J, Su R, Zheng R, Xing F, Zhang Y, Wang N, Chen H, Feng S. Predicting effect of anti-PD-1/PD-L1 inhibitors therapy for hepatocellular carcinoma by detecting plasma metabolite based on UHPLC-MS. Front Immunol 2024; 15:1370771. [PMID: 38707906 PMCID: PMC11067499 DOI: 10.3389/fimmu.2024.1370771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
Introduction Anti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy. Methods Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS. Results A partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy. Discussion This study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.
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Affiliation(s)
- Botong Liu
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
| | - Jinyu Shi
- The Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Rui Su
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
| | - Ran Zheng
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
| | - Fan Xing
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
| | - Yuan Zhang
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
| | - Nanya Wang
- The Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Huanwen Chen
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Shouhua Feng
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, China
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Xu T, Li H, Dou P, Luo Y, Pu S, Mu H, Zhang Z, Feng D, Hu X, Wang T, Tan G, Chen C, Li H, Shi X, Hu C, Xu G. Concentric Hybrid Nanoelectrospray Ionization-Atmospheric Pressure Chemical Ionization Source for High-Coverage Mass Spectrometry Analysis of Single-Cell Metabolomics. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2306659. [PMID: 38359005 PMCID: PMC11040340 DOI: 10.1002/advs.202306659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 02/04/2024] [Indexed: 02/17/2024]
Abstract
High-coverage mass spectrometry analysis of single-cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra-small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization-atmospheric pressure chemical ionization (nanoESI-APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL-1. After the operational parameter optimization, 254 metabolites detected in nanoESI-APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI-APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI-APCI not only opens a new avenue for high-coverage and high-sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.
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Affiliation(s)
- Tianrun Xu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Hang Li
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Peng Dou
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Yuanyuan Luo
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Siming Pu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Hua Mu
- The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning116023P. R. China
| | - Zhihao Zhang
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of ScienceDalian Key Laboratory for Online Analytical InstrumentationDalianLiaoning116023P. R. China
| | - Disheng Feng
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Xuesen Hu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Ting Wang
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Guang Tan
- The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning116023P. R. China
| | - Chuang Chen
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of ScienceDalian Key Laboratory for Online Analytical InstrumentationDalianLiaoning116023P. R. China
| | - Haiyang Li
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of ScienceDalian Key Laboratory for Online Analytical InstrumentationDalianLiaoning116023P. R. China
| | - Xianzhe Shi
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Chunxiu Hu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of Sciences (CAS)University of Chinese Academy of SciencesLiaoning Province Key Laboratory of MetabolomicsDalianLiaoning116023P. R. China
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Song G, Wang L, Tang J, Li H, Pang S, Li Y, Liu L, Hu J. Circulating metabolites as potential biomarkers for the early detection and prognosis surveillance of gastrointestinal cancers. Metabolomics 2023; 19:36. [PMID: 37014438 PMCID: PMC10073066 DOI: 10.1007/s11306-023-02002-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/22/2023] [Indexed: 04/05/2023]
Abstract
BACKGROUND AND AIMS Two of the most lethal gastrointestinal (GI) cancers, gastric cancer (GC) and colon cancer (CC), are ranked in the top five cancers that cause deaths worldwide. Most GI cancer deaths can be reduced by earlier detection and more appropriate medical treatment. Unlike the current "gold standard" techniques, non-invasive and highly sensitive screening tests are required for GI cancer diagnosis. Here, we explored the potential of metabolomics for GI cancer detection and the classification of tissue-of-origin, and even the prognosis management. METHODS Plasma samples from 37 gastric cancer (GC), 17 colon cancer (CC), and 27 non-cancer (NC) patients were prepared for metabolomics and lipidomics analysis by three MS-based platforms. Univariate, multivariate, and clustering analyses were used for selecting significant metabolic features. ROC curve analysis was based on a series of different binary classifications as well as the true-positive rate (sensitivity) and the false-positive rate (1-specificity). RESULTS GI cancers exhibited obvious metabolic perturbation compared with benign diseases. The differentiated metabolites of gastric cancer (GC) and colon cancer (CC) were targeted to same pathways but with different degrees of cellular metabolism reprogramming. The cancer-specific metabolites distinguished the malignant and benign, and classified the cancer types. We also applied this test to before- and after-surgery samples, wherein surgical resection significantly altered the blood-metabolic patterns. There were 15 metabolites significantly altered in GC and CC patients who underwent surgical treatment, and partly returned to normal conditions. CONCLUSION Blood-based metabolomics analysis is an efficient strategy for GI cancer screening, especially for malignant and benign diagnoses. The cancer-specific metabolic patterns process the potential for classifying tissue-of-origin in multi-cancer screening. Besides, the circulating metabolites for prognosis management of GI cancer is a promising area of research.
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Affiliation(s)
- Guodong Song
- The Second Hospital of Tianjin Medical University, No 23. Pingjiang Road, Hexi District, 300211, Tianjin, China
| | - Li Wang
- The Second Hospital of Tianjin Medical University, No 23. Pingjiang Road, Hexi District, 300211, Tianjin, China
| | - Junlong Tang
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Haohui Li
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Shuyu Pang
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Yan Li
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Li Liu
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China.
| | - Junyuan Hu
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China.
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Wu X, Wang Z, Luo L, Shu D, Wang K. Metabolomics in hepatocellular carcinoma: From biomarker discovery to precision medicine. FRONTIERS IN MEDICAL TECHNOLOGY 2023; 4:1065506. [PMID: 36688143 PMCID: PMC9845953 DOI: 10.3389/fmedt.2022.1065506] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 12/06/2022] [Indexed: 01/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains a global health burden, and is mostly diagnosed at late and advanced stages. Currently, limited and insensitive diagnostic modalities continue to be the bottleneck of effective and tailored therapy for HCC patients. Moreover, the complex reprogramming of metabolic patterns during HCC initiation and progression has been obstructing the precision medicine in clinical practice. As a noninvasive and global screening approach, metabolomics serves as a powerful tool to dynamically monitor metabolic patterns and identify promising metabolite biomarkers, therefore holds a great potential for the development of tailored therapy for HCC patients. In this review, we summarize the recent advances in HCC metabolomics studies, including metabolic alterations associated with HCC progression, as well as novel metabolite biomarkers for HCC diagnosis, monitor, and prognostic evaluation. Moreover, we highlight the application of multi-omics strategies containing metabolomics in biomarker discovery for HCC. Notably, we also discuss the opportunities and challenges of metabolomics in nowadays HCC precision medicine. As technologies improving and metabolite biomarkers discovering, metabolomics has made a major step toward more timely and effective precision medicine for HCC patients.
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Affiliation(s)
- Xingyun Wu
- West China School of Basic Medical Science & Forensic Medicine, Sichuan University, Chengdu, China
| | - Zihao Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Li Luo
- Center for Reproductive Medicine, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Dan Shu
- School of Bioscience and Technology, Chengdu Medical College, Chengdu, China,Correspondence: Kui Wang Dan Shu
| | - Kui Wang
- West China School of Basic Medical Science & Forensic Medicine, Sichuan University, Chengdu, China,Correspondence: Kui Wang Dan Shu
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Ouyang R, Ding J, Huang Y, Zheng F, Zheng S, Ye Y, Li Q, Wang X, Ma X, Zou Y, Chen R, Zhuo Z, Li Z, Xin Q, Zhou L, Lu X, Ren Z, Liu X, Kovatcheva-Datchary P, Xu G. Maturation of the gut metabolome during the first year of life in humans. Gut Microbes 2023; 15:2231596. [PMID: 37424334 PMCID: PMC10334852 DOI: 10.1080/19490976.2023.2231596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 06/23/2023] [Accepted: 06/27/2023] [Indexed: 07/11/2023] Open
Abstract
The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of Bacteroides in the Swedish cohort and Streptococcus in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as Bacteroides vulgatus and Parabacteroides merdae. Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.
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Affiliation(s)
- Runze Ouyang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Juan Ding
- Department of Quality Control, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Huang
- University of Chinese Academy of Sciences, Beijing, China
| | - Fujian Zheng
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Sijia Zheng
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Yaorui Ye
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Qi Li
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Xiaolin Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Xiao Ma
- Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuxin Zou
- Department of Pediatrics, Liaocheng People’s Hospital, Liaocheng, China
| | - Rong Chen
- Department of Respiratory Medicine, Dalian Municipal Women and Children’s Medical Center (Group), Dalian, China
| | - Zhihong Zhuo
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhen Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qi Xin
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Lina Zhou
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Xin Lu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinyu Liu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
| | - Petia Kovatcheva-Datchary
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Molecular Infection Biology, University of Wurzburg, Wurzburg, Germany
- Department of Pediatrics, University of Wurzburg, Wurzburg, Germany
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
- University of Chinese Academy of Sciences, Beijing, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
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Ding J, Ouyang R, Zheng S, Wang Y, Huang Y, Ma X, Zou Y, Chen R, Zhuo Z, Li Z, Xin Q, Zhou L, Mei S, Yan J, Lu X, Ren Z, Liu X, Xu G. Effect of Breastmilk Microbiota and Sialylated Oligosaccharides on the Colonization of Infant Gut Microbial Community and Fecal Metabolome. Metabolites 2022; 12:1136. [PMID: 36422276 PMCID: PMC9698434 DOI: 10.3390/metabo12111136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/09/2022] [Accepted: 11/16/2022] [Indexed: 07/30/2023] Open
Abstract
The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3'-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk-gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome.
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Affiliation(s)
- Juan Ding
- Department of Quality Control, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Runze Ouyang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Sijia Zheng
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Yanfeng Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Yan Huang
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiao Ma
- Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yuxin Zou
- Liaocheng People’s Hospital, Liaocheng 252000, China
| | - Rong Chen
- Dalian Municipal Women and Children’s Medical Center (Group), Dalian 116011, China
| | - Zhihong Zhuo
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhen Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Qi Xin
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China
| | - Lina Zhou
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Surong Mei
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jingyu Yan
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
| | - Xin Lu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Xinyu Liu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
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Wang N, Yang L, Shang L, Liang Z, Wang Y, Feng M, Yu S, Li X, Gao C, Li Z, Luo J. Altered Fecal Metabolomics and Potential Biomarkers of Psoriatic Arthritis Differing From Rheumatoid Arthritis. Front Immunol 2022; 13:812996. [PMID: 35296075 PMCID: PMC8919725 DOI: 10.3389/fimmu.2022.812996] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/31/2022] [Indexed: 11/13/2022] Open
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.
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Affiliation(s)
- Nan Wang
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Linjiao Yang
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China
| | - Lili Shang
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhaojun Liang
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Yanlin Wang
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Min Feng
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Shuting Yu
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China
| | - Xiaoying Li
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China
| | - Chong Gao
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Zhenyu Li
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China
| | - Jing Luo
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China
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Nenu I, Stefanescu H, Procopet B, Sparchez Z, Minciuna I, Mocan T, Leucuta D, Morar C, Grigorescu M, Filip GA, Socaciu C. Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis. J Clin Med 2022; 11:1292. [PMID: 35268381 PMCID: PMC8910918 DOI: 10.3390/jcm11051292] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/19/2022] [Accepted: 02/24/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients—32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0−0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine.
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Affiliation(s)
- Iuliana Nenu
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Horia Stefanescu
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Bogdan Procopet
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Zeno Sparchez
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Iulia Minciuna
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Tudor Mocan
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Daniel Leucuta
- Department of Medical Statistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Corina Morar
- Center for Applied Biotechnology BIODIATECH, SC Proplanta, 400478 Cluj-Napoca, Romania; (C.M.); (C.S.)
| | - Mircea Grigorescu
- 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (B.P.); (Z.S.); (I.M.); (T.M.); (M.G.)
- Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Gabriela Adriana Filip
- Department of Physiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Carmen Socaciu
- Center for Applied Biotechnology BIODIATECH, SC Proplanta, 400478 Cluj-Napoca, Romania; (C.M.); (C.S.)
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9
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Li C, Gao Z, Su B, Xu G, Lin X. Data analysis methods for defining biomarkers from omics data. Anal Bioanal Chem 2021; 414:235-250. [PMID: 34951658 DOI: 10.1007/s00216-021-03813-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/26/2021] [Accepted: 11/29/2021] [Indexed: 02/01/2023]
Abstract
Omics mainly includes genomics, epigenomics, transcriptomics, proteomics and metabolomics. The rapid development of omics technology has opened up new ways to study disease diagnosis and prognosis and to define prospective information of complex diseases. Since omics data are usually large and complex, the method used to analyze the data and to define important information is crucial in omics study. In this review, we focus on advances in biomarker discovery methods based on omics data in the last decade, and categorize them as individual feature analysis, combinatorial feature analysis and network analysis. We also discuss the challenges and perspectives in this field.
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Affiliation(s)
- Chao Li
- School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
| | - Zhenbo Gao
- School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Benzhe Su
- School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
| | - Xiaohui Lin
- School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China.
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10
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Jiang H, Li L, Chen W, Chen B, Li H, Wang S, Wang M, Luo Y. Application of Metabolomics to Identify Potential Biomarkers for the Early Diagnosis of Coronary Heart Disease. Front Physiol 2021; 12:775135. [PMID: 34912241 PMCID: PMC8667077 DOI: 10.3389/fphys.2021.775135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/09/2021] [Indexed: 11/15/2022] Open
Abstract
Coronary heart disease (CHD) is one of the leading causes of deaths globally. Identification of serum metabolic biomarkers for its early diagnosis is thus much desirable. Serum samples were collected from healthy controls (n = 86) and patients with CHD (n = 166) and subjected to untargeted and targeted metabolomics analyses. Subsequently, potential biomarkers were detected and screened, and a clinical model was developed for diagnosing CHD. Four dysregulated metabolites, namely PC(17:0/0:0), oxyneurine, acetylcarnitine, and isoundecylic acid, were identified. Isoundecylic acid was not found in Human Metabolome Database, so we could not validate differences in its relative abundance levels. Further, the clinical model combining serum oxyneurine, triglyceride, and weight was found to be more robust than that based on PC(17:0/0:0), oxyneurine, and acetylcarnitine (AUC = 0.731 vs. 0.579, sensitivity = 83.0 vs. 75.5%, and specificity = 64.0 vs. 46.5%). Our findings indicated that serum metabolomics is an effective method to identify differential metabolites and that serum oxyneurine, triglyceride, and weight appear to be promising biomarkers for the early diagnosis of CHD.
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Affiliation(s)
- Huali Jiang
- Department of Cardiovascularology, The First Affiliated Hospital of Jinan University, Guangzhou, China.,Department of Cardiovascularology, Dongguan Tungwah Hospital, Dongguan, China
| | - Li Li
- Department of Cardiovascularology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Weijie Chen
- Department of Cardiovascularology, Dongguan Tungwah Hospital, Dongguan, China
| | - Benfa Chen
- Department of Cardiovascularology, Dongguan Tungwah Hospital, Dongguan, China
| | - Heng Li
- Department of Cardiovascularology, Dongguan Tungwah Hospital, Dongguan, China
| | - Shanhua Wang
- Department of Cardiovascularology, Dongguan Tungwah Hospital, Dongguan, China
| | - Min Wang
- Department of Cardiovascularology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yi Luo
- Department of Cardiovascularology, The First Affiliated Hospital of Jinan University, Guangzhou, China.,Department of Cardiovascularology, Guangzhou First People's Hospital, Guangzhou, China
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11
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Jiang CH, Lin PF, Chen FC, Chen JY, Xie WJ, Li M, Hu XJ, Chen WL, Cheng Y, Lin XX. Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study. J Proteome Res 2021; 21:822-832. [PMID: 34319108 DOI: 10.1021/acs.jproteome.1c00430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.
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Affiliation(s)
- Cheng-Hong Jiang
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China.,Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou 35001, China.,Tissue and Organ Regeneration Engineering Center of Fujian Higher Education, Fuzhou 350001, China
| | - Peng-Fei Lin
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Fa-Chun Chen
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Jia-Yao Chen
- Department of Plastic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 51000, China
| | - Wen-Jun Xie
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Ming Li
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Xiao-Jie Hu
- Department of Plastic and Reconstruction Surgery, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200010, China
| | - Wen-Lian Chen
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yu Cheng
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.,School of Pharmacy, Shanghai Jiao Tong University Shanghai, 200240, China
| | - Xiao-Xi Lin
- Department of Plastic and Reconstruction Surgery, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200010, China
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12
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Guan MC, Ouyang W, Wang MD, Liang L, Li N, Fu TT, Shen F, Lau WY, Xu QR, Huang DS, Zhu H, Yang T. Biomarkers for hepatocellular carcinoma based on body fluids and feces. World J Gastrointest Oncol 2021; 13:351-365. [PMID: 34040698 PMCID: PMC8131906 DOI: 10.4251/wjgo.v13.i5.351] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/18/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.
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Affiliation(s)
- Ming-Cheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Wei Ouyang
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Na Li
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ting-Ting Fu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
| | - Wan-Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Qiu-Ran Xu
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Dong-Sheng Huang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
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13
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Fang C, Su B, Jiang T, Li C, Tan Y, Wang Q, Dong L, Liu X, Lin X, Xu G. Prognosis prediction of hepatocellular carcinoma after surgical resection based on serum metabolic profiling from gas chromatography-mass spectrometry. Anal Bioanal Chem 2021; 413:3153-3165. [PMID: 33796932 DOI: 10.1007/s00216-021-03281-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/26/2021] [Accepted: 03/08/2021] [Indexed: 01/27/2023]
Abstract
Comprehensive prognostic risk prediction of hepatocellular carcinoma (HCC) after surgical treatment is particularly important for guiding clinical decision-making and improving postoperative survival. Hence, we aimed to build prognostic models based on serum metabolomics data, and assess the prognostic risk of HCC within 5 years after surgical resection. A pseudotargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics method was applied to analyze serum profiling of 78 HCC patients. Important metabolic features with discriminant ability were identified by a novel network-based metabolic feature selection method based on combinational significance index (N-CSI). Subsequently, phenylalanine and galactose were further identified to be relevant with mortality by the Cox regression analysis, while galactose and tyrosine were associated with recurrence and metastasis. Two models to predict risk of mortality (risk score of overall survival, RSOS) and risk of recurrence and metastasis (risk score of disease-free survival, RSDFS) were generated based on two panels of metabolites, respectively, which present favorable ability to predict prognosis of HCC, especially when combined with clinical staging system. The performance of models was further validated in an external independent cohort from 91 HCC patients. This study demonstrated that metabolomics is a powerful tool for risk screening of HCC prognosis.
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Affiliation(s)
- Chengnan Fang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Benzhe Su
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Tianyi Jiang
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China
| | - Chao Li
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China
| | - Yexiong Tan
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China
| | - Qingqing Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
| | - Liwei Dong
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, 200438, China.
| | - Xinyu Liu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China.
| | - Xiaohui Lin
- School of Computer Science & Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China.
| | - Guowang Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China
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