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Cai R, Ke L, Zhao Y, Zhao J, Zhang H, Zheng P, Xin L, Ma C, Lin Y. NMR-based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages. Int J Cancer 2025; 156:1644-1655. [PMID: 39629979 PMCID: PMC11826128 DOI: 10.1002/ijc.35273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 10/15/2024] [Accepted: 10/23/2024] [Indexed: 02/16/2025]
Abstract
Colorectal cancer (CRC) still remains the leading cause of cancer death worldwide. This study aimed to profile the metabolic differences of colorectal cancer tissues (CCT) at different stages and sites, as compared with their distant noncancerous tissues (DNT), to investigate the temporal and spatial heterogeneities of metabolic characterization. Our NMR-based metabolomics fingerprinting revealed that many of the metabolite levels were significantly altered in CCT compared to DNT and esophageal cancer tissues, indicating deregulations of glucose metabolism, one-carbon metabolism, glutamine metabolism, amino acid metabolism, fatty acid metabolism, TCA cycle, choline metabolism, and so forth. A total of five biomarker metabolites, including glucose, glutamate, alanine, valine and histidine, were identified to distinguish between early and advanced stages of CCT. Metabolites that distinguish the different anatomical sites of CCT include glucose, glycerol, glutamine, inositol, succinate, and citrate. Those significant metabolic differences in CRC tissues at different pathological stages and sites suggested temporal and spatial heterogeneities of metabolic characterization in CCT, providing a metabolic foundation for further study on biofluid metabolism in CRC early detection.
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Affiliation(s)
- Rongzhi Cai
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - LiXin Ke
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - Yan Zhao
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - Jiayun Zhao
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - Huanian Zhang
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - Peie Zheng
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
| | - Lijing Xin
- Animal Imaging and Technology Core, Center for Biomedical ImagingEcole Polytechnique Fédérale de LausanneLausanneSwitzerland
| | - Changchun Ma
- Radiation Oncology DepartmentCancer Hospital of Shantou University Medical CollegeShantouGuangdongChina
| | - Yan Lin
- Radiology Department, Second Affiliated HospitalShantou University Medical CollegeShantou CityGuangdong ProvinceChina
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Șaitiș LR, Andras D, Pop IA, Șaitiș C, Crainic R, Fechete R. Spectroscopic Nuclear Magnetic Resonance and Fourier Transform-Infrared Approach Used for the Evaluation of Healing After Surgical Interventions for Patients with Colorectal Cancer: A Pilot Study. Cancers (Basel) 2025; 17:887. [PMID: 40075738 PMCID: PMC11899188 DOI: 10.3390/cancers17050887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/01/2025] [Accepted: 03/03/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: Colorectal cancer (CRC) is one of the most common and deadly types of cancer. Compared with the classical histopathological approach, this study discusses the application of 1H NMR and FT-IR techniques for the fast evaluation degree of healing of patients with CRC after surgical intervention. Methods: Native and deproteinized blood plasma collected from 10 patients with confirmed CRC and 20 healthy volunteers were analyzed using 1H NMR T2 distributions and FT-IR spectra measured for samples collected before and 7 days after surgery. The average FT-IR spectrum from 20 healthy volunteers is also presented. Principal component analysis (PCA) was performed on the FT-IR spectra. The results were used for further statistical analysis using receiver operating characteristic (ROC) and area under the curve (AUC) and to produce a series of prediction maps using a machine learning library. Results: Both experimental methods combined with analysis methods demonstrated that the native blood plasma samples can be better used to predict the CRC patients' evolution 7 days after surgery. Three patients showed a significant evolution by 1H NMR T2 distribution, correlated to the observation of FT-IR-PCA analysis. Maps of medical state probability were generated using a trained machine learning-based ANN. Conclusions: The experimental measurements combined with an advanced statistical analysis and machine learning were successfully used and show that the healing process of patients with CRC is not linear, from the preoperative state to the state associated with healthy volunteers, but passes through a distinct healing state.
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Affiliation(s)
- Lavinia Raluca Șaitiș
- Doctoral School, Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084 Cluj-Napoca, Romania or (L.R.Ș.); or (R.C.)
- Faculty of Material and Environmental Engineering, Technical University of Cluj-Napoca, 103-105 Muncii Bulevard, 400641 Cluj-Napoca, Romania
| | - David Andras
- Surgical Department, County Emergency Hospital, Clinicilor Str. 3-5, 400009 Cluj-Napoca, Romania;
- Surgical Department, Faculty of General Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Victor Babeș Str. 8, 400012 Cluj-Napoca, Romania
| | - Ioana-Alina Pop
- Radiology Department, County Emergency Hospital, Clinicilor Str. 3-5, 400009 Cluj-Napoca, Romania;
| | - Cătălin Șaitiș
- Faculty of Construction, Technical University of Cluj-Napoca, 25 Barițiu, 400641 Cluj-Napoca, Romania;
| | - Ramona Crainic
- Doctoral School, Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084 Cluj-Napoca, Romania or (L.R.Ș.); or (R.C.)
- Faculty of Material and Environmental Engineering, Technical University of Cluj-Napoca, 103-105 Muncii Bulevard, 400641 Cluj-Napoca, Romania
| | - Radu Fechete
- Faculty of Material and Environmental Engineering, Technical University of Cluj-Napoca, 103-105 Muncii Bulevard, 400641 Cluj-Napoca, Romania
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Samad MA, Zamani AI, Abdul Majid N, Karsani SA, Baharum SN, Yaacob JS, Saiman MZ. An Integrative Approach Using Molecular and Metabolomic Studies Reveals the Connection of Glutamic Acid with Telomerase and Oxidative Stress in Berberine-Treated Colorectal Cancer Cell Line HCT 116. Appl Biochem Biotechnol 2025:10.1007/s12010-025-05200-9. [PMID: 40009339 DOI: 10.1007/s12010-025-05200-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2025] [Indexed: 02/27/2025]
Abstract
Colorectal cancer (CRC) is one of the common deadliest cancers worldwide. In Malaysia, the numbers of new CRC cases were horrific and worrisome. Telomerase is both prognostic indicator and predictor of carcinogenesis in CRC patients. Berberine, a telomerase inhibitor, was used in clinical trials and metabolomic studies; however, the association of telomerase with metabolites and metabolic pathways was not fully understood. Colorectal cancer cell line HCT 116 was cultured and treated with 10.54 µg/mL berberine. The cells were harvested at different time points to conduct subsequent analyses. The methods used in this research were real time-polymerase chain reaction (RT-PCR) to assess RNA expressions; Western blot to determine protein levels; TELOTAGGG Telomerase PCR ELISA to determine relative telomerase activity (RTA); 4',6-diamidino-2-phenylindole (DAPI) staining to determine percentage of nuclei damage; fluorescence microscopy for cell area; spectrophotometric potassium iodide assay for intracellular hydrogen peroxide concentration [H2O2]; as well as liquid chromatography mass spectrometry (LCMS) and tandem mass spectrometry (MS/MS) to investigate the intracellular metabolites. Partial least square-discriminant analysis (PLS-DA) score plot exhibited an improved separation compared to principal component analysis (PCA) when metabolomic data analysis of HCT 116 at various berberine treatment durations was conducted. Time and berberine treatment had an impact on RTA in HCT 116. RTA was discovered to be positively and negatively correlated to 14 and 2 metabolites, respectively. Glutamic acid was consistently found correlated to RTA. Other four metabolites, i.e., MG(14:0), [3-[hydroxy(phosphonooxy)phosphoryl]oxyphenyl] phosphono hydrogen phosphate), (3S,6S)-6-[[(3S,6R)-6-[(2S,3S,5S)-2,5-diiodo-4-methoxy-6-methyloxan-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid, and 1-[5-O-(5'-adenylyloxyphosphonyl)-beta-D-ribofuranosyl]-5-amino-1H-imidazole-4-carboxamide, were newly discovered to be connected to RTA in HCT 116. Four metabolic pathways that majorly affected shared glutamic acid and glutamine. Nitrogen metabolism, D-glutamine and D-glutamate metabolism, glyoxylate and dicarboxylate metabolism, and aminoacyl-tRNA biosynthesis have been identified to be associated with RTA. Network analyses hinted that glutamic acid was also associated with oxidative stress mechanism. The multiple roles glutamic acid acted in diverse metabolic pathways and interaction networks emphasized the importance of glutamic acid in HCT 116 regarding RTA. This research establishes the association between RTA and several chosen RNAs, proteins, metabolites, and oxidative stress mechanisms, consequential in morphological alteration in HCT 116, to expand the knowledge of the intricate biological relationships and telomerase mechanism in CRC.
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Affiliation(s)
- Muhammad Azizan Samad
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
- INFRA High Impact Research (HIR), HIR Building, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Arief Izzairy Zamani
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
| | - Nazia Abdul Majid
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Saiful Anuar Karsani
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Syarul Nataqain Baharum
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia
| | - Jamilah Syafawati Yaacob
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
| | - Mohd Zuwairi Saiman
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
- Centre for Natural Products Research and Drug Discovery (CENAR), Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
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Duan C, Sheng J, Ma X. Innovative approaches in colorectal cancer screening: advances in detection methods and the role of artificial intelligence. Therap Adv Gastroenterol 2025; 18:17562848251314829. [PMID: 39898356 PMCID: PMC11783499 DOI: 10.1177/17562848251314829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 01/06/2025] [Indexed: 02/04/2025] Open
Abstract
Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.
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Affiliation(s)
- Changwei Duan
- Medical School of Chinese PLA, Beijing, China Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jianqiu Sheng
- Medical School of Chinese PLA, Beijing 100853, China Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Beijing 100700, China
| | - Xianzong Ma
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100700, China
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Abu Bakar MF, Mohammed Nawi A, Chin SF, Makpol S. Current status of serum metabolites biomarkers for polyps and colorectal cancer: a systematic review. Gastroenterol Rep (Oxf) 2024; 12:goae106. [PMID: 39678161 PMCID: PMC11646065 DOI: 10.1093/gastro/goae106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 11/17/2024] [Accepted: 11/27/2024] [Indexed: 12/17/2024] Open
Abstract
Background Early detection of colorectal cancer (CRC) is crucial to enhance the disease treatment and prognosis of patients. Colonoscopy remains the gold standard for CRC detection; however, it requires trained personnel with expensive tools. Currently, serum metabolites have been discovered to be used to discriminate patients with polyps and CRC. This study aimed to identify the most commonly detected predictive serum metabolites for polyps and CRC. Methods A systematic search of the Web of Science, PubMed, and Cochrane Library databases was conducted using PRISMA guidelines. Ten studies investigating serum metabolite biomarkers of CRC and polyps using different analytical platforms and study populations were included. QUADOMICS tool was used to analyse the quality of the included studies. All reported metabolites were then enriched into the pathways using MetaboAnalyst 5.0. Results We found that several potential signature metabolites overlapped between studies, including tyrosine, lysine, cystine, arabinose, and lactate for CRC and lactate and glutamate for polyps. The most affected pathways related to CRC were the urea cycle, glutathione metabolism, purine metabolism, glutamate metabolism, and ammonia recycling. In contrast, those affected in the polyps were the urea cycle, glutamate metabolism, glutathione metabolism, arginine and proline metabolism, and carnitine synthesis. Conclusions This review has found commonly detected serum metabolites for polyps and CRC with huge potential to be used in clinical settings. However, the differences between altered pathways in polyps and CRC, other external factors, and their effects on the regulation level, sensitivity, and specificity of each identified metabolite remained unclear, which could benefit from a further extensive cohort study and well-defined analysis equipment.
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Affiliation(s)
- Maryam Fatimah Abu Bakar
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Azmawati Mohammed Nawi
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Siok Fong Chin
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Cheras, Kuala Lumpur, Malaysia
| | - Suzana Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
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6
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Liang Y, Li Y, Lee C, Yu Z, Chen C, Liang C. Ulcerative colitis: molecular insights and intervention therapy. MOLECULAR BIOMEDICINE 2024; 5:42. [PMID: 39384730 PMCID: PMC11464740 DOI: 10.1186/s43556-024-00207-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/13/2024] [Indexed: 10/11/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. Current treatments for UC include 5-aminosalicylic acids, corticosteroids, immunosuppressants, and biologics. However, study reported that the one-year clinical remission rate is only around 40%. It is necessary to prompt the exploration of new treatment modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody and JAK inhibitor, primarily consist of small molecules targeting specific pathways, effectively inducing and maintaining remission. Given the significant role of the gut microbiota, research into intestinal microecologics, such as probiotics and prebiotics, and fecal microbiota transplantation (FMT) shows promising potential in UC treatment. Additionally, medicinal herbs, such as chili pepper and turmeric, used in complementary therapy have shown promising results in UC management. This article reviews recent findings on the mechanisms of UC, including genetic susceptibility, immune cell dynamics and cytokine regulation, and gut microbiota alterations. It also discusses current applications of biologic therapy, herbal therapy, microecologics, and FMT, along with their prospects and challenges.
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Affiliation(s)
- Yuqing Liang
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
- Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Yang Li
- Department of Respiratory, Sichuan Integrative Medicine Hospital, Chengdu, 610042, China
| | - Chehao Lee
- Department of Traditional Chinese Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Ziwei Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Chongli Chen
- Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
| | - Chao Liang
- Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
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Abu Bakar MF, Chin SF, Makpol S, Tan JK, Mohammed Nawi A. Diagnostic performance of serum metabolites biomarker associated with colorectal adenoma: a systematic review. PeerJ 2024; 12:e18043. [PMID: 39314843 PMCID: PMC11418823 DOI: 10.7717/peerj.18043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 08/13/2024] [Indexed: 09/25/2024] Open
Abstract
Evidence on serum biomarkers as a non-invasive tool to detect colorectal adenoma (CRA) in the general population is quite promising. However, the sensitivity and specificity of these serum biomarkers in detecting disease are still questionable. This study aimed to systematically review the evidence on the diagnostic performance of serum biomarkers associated with CRA. Database searches on PubMed, Scopus, and WoS from January 2014 to December 2023 using PRISMA guidelines resulted in 4,380 citations, nine of which met inclusion criteria. The quality of these studies was assessed using the QUADOMICS tool. These studies reported on 77 individual/panel biomarkers which were further analysed to find associated altered pathways using MetaboAnlyst 5.0. Diagnostic accuracy analysis of these biomarkers was conducted by constructing a receiver operating characteristic (ROC) curve using their reported sensitivity and specificity. This review identified six potential serum metabolite biomarkers with 0.7
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Affiliation(s)
- Maryam Fatimah Abu Bakar
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Siok Fong Chin
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Cheras, Kuala Lumpur, Malaysia
| | - Suzana Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Jen Kit Tan
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Azmawati Mohammed Nawi
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
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Zakari S, Niels NK, Olagunju GV, Nnaji PC, Ogunniyi O, Tebamifor M, Israel EN, Atawodi SE, Ogunlana OO. Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review. Front Oncol 2024; 14:1405267. [PMID: 39132504 PMCID: PMC11313249 DOI: 10.3389/fonc.2024.1405267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 07/05/2024] [Indexed: 08/13/2024] Open
Abstract
Cancer remains a global health challenge, necessitating continuous advancements in diagnostic and treatment strategies. This review focuses on the utility of non-invasive biomarkers in cancer diagnosis and treatment, their role in early detection, disease monitoring, and personalized therapeutic interventions. Through a systematic review of the literature, we identified 45 relevant studies that highlight the potential of these biomarkers across various cancer types, such as breast, prostate, lung, and colorectal cancers. The non-invasive biomarkers discussed include liquid biopsies, epigenetic markers, non-coding RNAs, exosomal cargo, and metabolites. Notably, liquid biopsies, particularly those based on circulating tumour DNA (ctDNA), have emerged as the most promising method for early, non-invasive cancer detection due to their ability to provide comprehensive genetic and epigenetic information from easily accessible blood samples. This review demonstrates how non-invasive biomarkers can facilitate early cancer detection, accurate subtyping, and tailored treatment strategies, thereby improving patient outcomes. It underscores the transformative potential of non-invasive biomarkers in oncology, highlighting their application for enhancing early detection, survival rates, and treatment precision in cancer care. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023474749 PROSPERO, identifier CRD42023474749.
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Affiliation(s)
- Suleiman Zakari
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
- Covenant Applied Informatics and Communication - Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria
- Department of Biochemistry, College of Medicine, Federal University of Health Sciences Otukpo, Otukpo, Benue State, Nigeria
| | - Nguedia K. Niels
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
- Covenant Applied Informatics and Communication - Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria
- Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon
| | - Grace V. Olagunju
- Department of Molecular Biology, New Mexico State University, Las Cruces, NM, United States
| | - Precious C. Nnaji
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
| | - Oluwabusayo Ogunniyi
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
| | - Mercy Tebamifor
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
- Covenant Applied Informatics and Communication - Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria
| | - Emmanuel N. Israel
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
- Covenant Applied Informatics and Communication - Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria
| | - Sunday E. Atawodi
- Department of Biochemistry, Federal University Lokoja, Lokoja, Kogi State, Nigeria
| | - Olubanke Olujoke Ogunlana
- Department of Biochemistry, College of Science and Technology, Covenant University, Ota, Ogun State, Nigeria
- Covenant Applied Informatics and Communication - Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria
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Fan Y, Hu C, Xie X, Weng Y, Chen C, Wang Z, He X, Jiang D, Huang S, Hu Z, Liu F. Effects of diets on risks of cancer and the mediating role of metabolites. Nat Commun 2024; 15:5903. [PMID: 39003294 PMCID: PMC11246454 DOI: 10.1038/s41467-024-50258-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 07/02/2024] [Indexed: 07/15/2024] Open
Abstract
Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.
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Affiliation(s)
- Yi Fan
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
| | - Chanchan Hu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Xiaoxu Xie
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Yanfeng Weng
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Chen Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Zhaokun Wang
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
| | - Xueqiong He
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
| | - Dongxia Jiang
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
| | - Shaodan Huang
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China.
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, School of Public Health, Peking University, Beijing, China.
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.
| | - Fengqiong Liu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.
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Li S, Zheng Y, Yang Y, Yang H, Han C, Du P, Wang X, Yang H. Diagnosis and classification of intestinal diseases with urine by surface-enhanced Raman spectroscopy. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 312:124081. [PMID: 38422936 DOI: 10.1016/j.saa.2024.124081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/02/2024]
Abstract
Intestinal Disease (ID) is often characterized by clinical symptoms such as malabsorption, intestinal dysfunction, and injury. If treatment is not timely, it will increase the risk of cancer. Early diagnosis of ID is the key to cure it. There are certain limitations of the conventional diagnostic methods, such as low sensitivity and specificity. Therefore, development of a highly sensitive, non-invasive diagnostic method for ID is extremely important. Urine samples are easier to collect and more sensitive to changes in biomolecules than other pathological diagnostic samples such as tissue and blood. In this paper, a diagnostic method of ID with urine by surface-enhanced Raman spectroscopy (SERS) is proposed. A classification model between ID patients and healthy controls (HC) and a classification model between different pathological types of ID (i.e., benign intestinal disease (BID) and colorectal cancer (CRC)) are established. Here, 830 urine samples, including 100 HC, 443 BID, and 287 CRC, were investigated by SERS. The ID/HC classification model was developed by analyzing the SERS spectra of 150 ID and 100 HC, while BID/CRC classification model was built with 300 BID and 150 CRC patients by principal component analysis (PCA)-support vector machines (SVM). The two established models were internally verified by leave-one-out-cross-validation (LOOCV). Finally, the BID/CRC classification model was further evaluated by 143 BID and 137 CRC patients as an external test set. It shows that the accuracy of the classification model validated by the LOOCV for ID/HC and BID/CRC is 86.4% and 85.56%, respectively. And the accuracy of the BID/CRC classification model with external test set is 82.14%. It shows that high accuracy can be achieved with these two established classification models. It indicates that ID patients in the general population can be identified and BID and CRC patients can be further classified with measuring urine by SERS. It shows that the proposed diagnostic method and established classification models provide valuable information for clinicians to early diagnose ID patients and analyze different stages of ID.
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Affiliation(s)
- Silong Li
- School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Yuqing Zheng
- School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Yiheng Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Haojie Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Changpeng Han
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Peng Du
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Xiaolei Wang
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
| | - Huinan Yang
- School of Energy and Power Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
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11
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Yang R, Tsigelny IF, Kesari S, Kouznetsova VL. Colorectal Cancer Detection via Metabolites and Machine Learning. Curr Issues Mol Biol 2024; 46:4133-4146. [PMID: 38785522 PMCID: PMC11119033 DOI: 10.3390/cimb46050254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/25/2024] Open
Abstract
Today, colorectal cancer (CRC) diagnosis is performed using colonoscopy, which is the current, most effective screening method. However, colonoscopy poses risks of harm to the patient and is an invasive process. Recent research has proven metabolomics as a potential, non-invasive detection method, which can use identified biomarkers to detect potential cancer in a patient's body. The aim of this study is to develop a machine-learning (ML) model based on chemical descriptors that will recognize CRC-associated metabolites. We selected a set of metabolites found as the biomarkers of CRC, confirmed that they participate in cancer-related pathways, and used them for training a machine-learning model for the diagnostics of CRC. Using a set of selective metabolites and random compounds, we developed a range of ML models. The best performing ML model trained on Stage 0-2 CRC metabolite data predicted a metabolite class with 89.55% accuracy. The best performing ML model trained on Stage 3-4 CRC metabolite data predicted a metabolite class with 95.21% accuracy. Lastly, the best-performing ML model trained on Stage 0-4 CRC metabolite data predicted a metabolite class with 93.04% accuracy. These models were then tested on independent datasets, including random and unrelated-disease metabolites. In addition, six pathways related to these CRC metabolites were also distinguished: aminoacyl-tRNA biosynthesis; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; and alanine, aspartate, and glutamate metabolism. Thus, in this research study, we created machine-learning models based on metabolite-related descriptors that may be helpful in developing a non-invasive diagnosis method for CRC.
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Affiliation(s)
- Rachel Yang
- REHS Program, San Diego Supercomputer Center, University of California San Diego, MC 0505, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Igor F. Tsigelny
- San Diego Supercomputer Center, University of California San Diego, MC 0505, 9500 Gilman Drive, La Jolla, CA 92093, USA;
- BiAna, P.O. Box 2525, La Jolla, CA 92038, USA
- Department of Neurosciences, University of California San Diego, MC00505, 9500 Gilman Drive, La Jolla, CA 92093, USA
- CureScience Institute, 5820 Oberlin Drive, STE 202, San Diego, CA 92121, USA
| | - Santosh Kesari
- Pacific Neuroscience Institute, 2125 Arizona Avenue, Santa Monica, CA 90404, USA;
| | - Valentina L. Kouznetsova
- San Diego Supercomputer Center, University of California San Diego, MC 0505, 9500 Gilman Drive, La Jolla, CA 92093, USA;
- BiAna, P.O. Box 2525, La Jolla, CA 92038, USA
- CureScience Institute, 5820 Oberlin Drive, STE 202, San Diego, CA 92121, USA
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12
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Evin D, Evinová A, Baranovičová E, Šarlinová M, Jurečeková J, Kaplán P, Poláček H, Halašová E, Dušenka R, Briš L, Brožová MK, Sivoňová MK. Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer. Int J Mol Sci 2024; 25:2630. [PMID: 38473877 DOI: 10.3390/ijms25052630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 02/19/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n = 51) and BPH patients (n = 48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using a quantitative real-time polymerase chain reaction (qRT-PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a downregulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility for distinguishing of mCRPC from BPH.
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Affiliation(s)
- Daniel Evin
- Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
- Clinic of Nuclear Medicine, Jessenius Faculty of Medicine in Martin, University Hospital in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Andrea Evinová
- Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Eva Baranovičová
- Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Miroslava Šarlinová
- Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Jana Jurečeková
- Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Peter Kaplán
- Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Hubert Poláček
- Clinic of Nuclear Medicine, Jessenius Faculty of Medicine in Martin, University Hospital in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Erika Halašová
- Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Róbert Dušenka
- Clinic of Urology, Jessenius Faculty of Medicine in Martin, University Hospital in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Lukáš Briš
- Clinic of Urology, Jessenius Faculty of Medicine in Martin, University Hospital in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Martina Knoško Brožová
- Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Monika Kmeťová Sivoňová
- Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
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13
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Jayakrishnan T, Mariam A, Farha N, Rotroff DM, Aucejo F, Barot SV, Conces M, Nair KG, Krishnamurthi SS, Schmit SL, Liska D, Khorana AA, Kamath SD. Plasma metabolomic differences in early-onset compared to average-onset colorectal cancer. Sci Rep 2024; 14:4294. [PMID: 38383634 PMCID: PMC10881959 DOI: 10.1038/s41598-024-54560-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 02/14/2024] [Indexed: 02/23/2024] Open
Abstract
Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I-IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3-0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies.
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Affiliation(s)
- Thejus Jayakrishnan
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
| | - Arshiya Mariam
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, USA
- Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, USA
| | - Nicole Farha
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
| | - Daniel M Rotroff
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, USA
- Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, USA
| | - Federico Aucejo
- Department of Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, USA
| | - Shimoli V Barot
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
- Case Comprehensive Cancer Center, Cleveland, USA
| | - Madison Conces
- Case Comprehensive Cancer Center, Cleveland, USA
- Department of Hematology-Oncology, University Hospital Seidman Cancer Center, Cleveland, USA
| | - Kanika G Nair
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
- Case Comprehensive Cancer Center, Cleveland, USA
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA
| | - Smitha S Krishnamurthi
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
- Case Comprehensive Cancer Center, Cleveland, USA
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA
| | - Stephanie L Schmit
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA
- Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, USA
- Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, USA
| | - David Liska
- Case Comprehensive Cancer Center, Cleveland, USA
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA
- Department of Colorectal Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, USA
| | - Alok A Khorana
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA
- Case Comprehensive Cancer Center, Cleveland, USA
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA
| | - Suneel D Kamath
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA.
- Case Comprehensive Cancer Center, Cleveland, USA.
- Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, USA.
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
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14
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Qiu X, Lu R, He Q, Chen S, Huang C, Lin D. Metabolic signatures and potential biomarkers for the diagnosis and treatment of colon cancer cachexia. Acta Biochim Biophys Sin (Shanghai) 2023; 55:1913-1924. [PMID: 37705348 PMCID: PMC11294056 DOI: 10.3724/abbs.2023151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 06/29/2023] [Indexed: 09/15/2023] Open
Abstract
Cancer cachexia (CAC) is a debilitating condition that often arises from noncachexia cancer (NCAC), with distinct metabolic characteristics and medical treatments. However, the metabolic changes and underlying molecular mechanisms during cachexia progression remain poorly understood. Understanding the progression of CAC is crucial for developing diagnostic approaches to distinguish between CAC and NCAC stages, facilitating appropriate treatment for cancer patients. In this study, we establish a mouse model of colon CAC and categorize the mice into three groups: CAC, NCAC and normal control (NOR). By performing nuclear magnetic resonance (NMR)-based metabolomic profiling on mouse sera, we elucidate the metabolic properties of these groups. Our findings unveil significant differences in the metabolic profiles among the CAC, NCAC and NOR groups, highlighting significant impairments in energy metabolism and amino acid metabolism during cachexia progression. Additionally, we observe the elevated serum levels of lysine and acetate during the transition from the NCAC to CAC stages. Using multivariate ROC analysis, we identify lysine and acetate as potential biomarkers for distinguishing between CAC and NCAC stages. These biomarkers hold promise for the diagnosis of CAC from noncachexia cancer. Our study provides novel insights into the metabolic mechanisms underlying cachexia progression and offers valuable avenues for the diagnosis and treatment of CAC in clinical settings.
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Affiliation(s)
- Xu Qiu
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Ruohan Lu
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Qiqing He
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Shu Chen
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Caihua Huang
- Research and Communication Center of Exercise and HealthXiamen University of TechnologyXiamen361005China
| | - Donghai Lin
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
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15
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Santos MD, Barros I, Brandão P, Lacerda L. Amino Acid Profiles in the Biological Fluids and Tumor Tissue of CRC Patients. Cancers (Basel) 2023; 16:69. [PMID: 38201497 PMCID: PMC10778074 DOI: 10.3390/cancers16010069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/19/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Amino acids are the building blocks of proteins and essential players in pathways such as the citric acid and urea cycle, purine and pyrimidine biosynthesis, and redox cell signaling. Therefore, it is unsurprising that these molecules have a significant role in cancer metabolism and its metabolic plasticity. As one of the most prevalent malign diseases, colorectal cancer needs biomarkers for its early detection, prognostic, and prediction of response to therapy. However, the available biomarkers for this disease must be more powerful and present several drawbacks, such as high costs and complex laboratory procedures. Metabolomics has gathered substantial attention in the past two decades as a screening platform to study new metabolites, partly due to the development of techniques, such as mass spectrometry or liquid chromatography, which have become standard practice in diagnostic procedures for other diseases. Extensive metabolomic studies have been performed in colorectal cancer (CRC) patients in the past years, and several exciting results concerning amino acid metabolism have been found. This review aims to gather and present findings concerning alterations in the amino acid plasma pool of colorectal cancer patients.
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Affiliation(s)
- Marisa Domingues Santos
- Colorectal Unit, Hospital de Santo António, Centro Hospitalar Universitário de Santo António, 4050-651 Porto, Portugal;
- UMIB—Unit for Multidisciplinary Research in Biomedicine, ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal; (I.B.); (L.L.)
- ITR—Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal
| | - Ivo Barros
- UMIB—Unit for Multidisciplinary Research in Biomedicine, ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal; (I.B.); (L.L.)
| | - Pedro Brandão
- Colorectal Unit, Hospital de Santo António, Centro Hospitalar Universitário de Santo António, 4050-651 Porto, Portugal;
- UMIB—Unit for Multidisciplinary Research in Biomedicine, ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal; (I.B.); (L.L.)
- ITR—Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal
| | - Lúcia Lacerda
- UMIB—Unit for Multidisciplinary Research in Biomedicine, ICBAS—School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal; (I.B.); (L.L.)
- ITR—Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal
- Genetic Laboratory Service, Centro de Genética Médica Jacinto de Magalhães, Centro Hospitalar Universitário de Santo António, 4050-651 Porto, Portugal
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16
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Alcolea JA, Donat-Vargas C, Chatziioannou AC, Keski-Rahkonen P, Robinot N, Molina AJ, Amiano P, Gómez-Acebo I, Castaño-Vinyals G, Maitre L, Chadeau-Hyam M, Dagnino S, Cheng SL, Scalbert A, Vineis P, Kogevinas M, Villanueva CM. Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain). ENVIRONMENTAL SCIENCE & TECHNOLOGY 2023; 57:19316-19329. [PMID: 37962559 PMCID: PMC11457144 DOI: 10.1021/acs.est.3c05814] [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: 07/20/2023] [Revised: 10/25/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023]
Abstract
We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation. Linear regression and partial least-squares analyses were conducted for chloroform, brominated THMs, total THMs, and nitrate among controls and for case-control status, together with a N-integration model discriminating colorectal cancer cases from controls through interrogation of correlations between the exposure variables and the metabolomic features. Results revealed a total of 568 metabolomic features associated with at least one water contaminant or colorectal cancer. Annotated metabolites and pathway analysis suggest a number of pathways as potentially involved in the link between exposure to these water contaminants and colorectal cancer, including nicotinamide, cytochrome P-450, and tyrosine metabolism. These findings provide insights into the underlying biological mechanisms and potential biomarkers associated with water contaminant exposure and colorectal cancer risk. Further research in this area is needed to better understand the causal relationship and the public health implications.
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Affiliation(s)
- Jose A. Alcolea
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
| | - Carolina Donat-Vargas
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
- Unit
of Cardiovascular and Nutritional Epidemiology, Institute of Environmental
Medicine, Karolinska Institutet, Stockholm 17177, Sweden
| | | | - Pekka Keski-Rahkonen
- International
Agency for Research on Cancer, 25 avenue Tony Garnier, CS 90627 69366, Lyon, France
| | - Nivonirina Robinot
- International
Agency for Research on Cancer, 25 avenue Tony Garnier, CS 90627 69366, Lyon, France
| | - Antonio José Molina
- Research
Group in Gene - Environment and Health Interactions (GIIGAS)/Institute
of Biomedicine (IBIOMED), Universidad de
León, Campus Universitario
de Vegazana, León 24071, Spain
- Faculty
of Health Sciences, Department of Biomedical Sciences, Area of Preventive
Medicine and Public Health, Universidad
de León, Campus Universitario
de Vegazana, León 24071, Spain
| | - Pilar Amiano
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Ministry
of Health of the Basque Government, Sub Directorate for Public Health
and Addictions of Gipuzkoa; BioGipuzkoa
(BioDonostia) Health Research Institute, San Sebastián 20013, Spain
| | - Inés Gómez-Acebo
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universidad
de Cantabria-IDIVAL, Avenida Cardenal Herrera Oria S/N, Santander 39011, Spain
| | - Gemma Castaño-Vinyals
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
- IMIM (Hospital del Mar Medical Research Institute), c/Doctor Aiguader 88, Barcelona 08003, Spain
| | - Lea Maitre
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
| | - Marc Chadeau-Hyam
- MRC
Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United
Kingdom
| | - Sonia Dagnino
- MRC
Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United
Kingdom
- Transporters
in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine,
Direction de la Recherche Fondamentale (DRF), Institut des Sciences
du Vivant Frédéric Joliot, Commissariat à l’Energie
Atomique et aux Énergies Alternatives (CEA), Université Côte d’Azur (UCA), 28 Avenue de Valombrose, Nice 06107, France
| | - Sibo Lucas Cheng
- MRC
Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United
Kingdom
| | - Augustin Scalbert
- International
Agency for Research on Cancer, 25 avenue Tony Garnier, CS 90627 69366, Lyon, France
| | - Paolo Vineis
- MRC
Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United
Kingdom
| | - Manolis Kogevinas
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
- IMIM (Hospital del Mar Medical Research Institute), c/Doctor Aiguader 88, Barcelona 08003, Spain
| | - Cristina M. Villanueva
- ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain
- CIBER
Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5,
Pabellón 11, Planta 0, Madrid 28029, Spain
- Universitat
Pompeu Fabra (UPF), c/Doctor
Aiguader 88, Barcelona 08003, Spain
- IMIM (Hospital del Mar Medical Research Institute), c/Doctor Aiguader 88, Barcelona 08003, Spain
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17
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Chen H, Zhou H, Liang Y, Huang Z, Yang S, Wang X, She Z, Wei Z, Zhang Q. UHPLC-HRMS-based serum untargeted lipidomics: Phosphatidylcholines and sphingomyelins are the main disturbed lipid markers to distinguish colorectal advanced adenoma from cancer. J Pharm Biomed Anal 2023; 234:115582. [PMID: 37473505 DOI: 10.1016/j.jpba.2023.115582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/02/2023] [Accepted: 07/12/2023] [Indexed: 07/22/2023]
Abstract
Colorectal advanced adenoma (CAA) is a key precancerous lesion of colorectal cancer (CRC), and early diagnosis can lessen CRC morbidity and mortality. Although abnormal lipid metabolism is associated with the development of CRC, there are no studies on the biomarkers and mechanism of lipid metabolism linked to CAA carcinogenesis. Hence, we performed a lipidomics study of serum samples from 46 CAA, and 50 CRC patients by the ultra high-performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) in both electrospray ionization (ESI) modes. Differential lipids were selected by univariate and multivariate statistics analysis, and their diagnostic performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Combining P < 0.05 and variable importance in projection (VIP) > 1, 59 differential lipids were obtained totally. Ten of them showed good discriminant ability for CAA and CRC (AUC > 0.900). Especially, the lipid panel consisting of PC 44:5, PC 35:6e, and SM d40:3 showed the highest selection frequency and outperformed (AUC = 0.952). Additionally, phosphatidylcholine (PC) and sphingomyelin (SM) were the main differential and high-performance lipids. In short, this is the first study to explore the biomarkers and mechanism for CAA-CRC sequence with large-scale serum lipidomics. The findings should provide valuable reference and new clues for the development of diagnostic and therapeutic strategies of CRC.
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Affiliation(s)
- Hongwei Chen
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Hailin Zhou
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Yunxiao Liang
- Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, PR China
| | - Zongsheng Huang
- Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, PR China
| | - Shanyi Yang
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Xuancheng Wang
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Zhiyong She
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Zhijuan Wei
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China
| | - Qisong Zhang
- Medical College, Guangxi University, Nanning, Guangxi 530004, PR China; Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Hubei Minzu University, Enshi, Hubei 44500, PR China; Center for Instrumental Analysis, Guangxi University, Nanning, Guangxi 530004, PR China.
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18
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Liu T, Liu C, Song M, Wei Y, Song Y, Chen P, Liu L, Wang B, Shi H. The association of serum serine levels with the risk of incident cancer: results from a nested case-control study. Food Funct 2023; 14:7969-7976. [PMID: 37578153 DOI: 10.1039/d3fo00808h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
Background: Cancer is associated with the dysregulation of serum serine levels, and tumor growth is supported by increased serine biosynthesis. This study aims to explore the association of serum serine levels with incident cancer risk in Chinese hypertensive adults. Materials and methods: 1391 patients with incident cancer and 1391 matched controls in terms of age, sex, and residence with cases in a 1 : 1 ratio were included in this nested case-control study. The serum serine concentrations were determined by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS) at the baseline. The associations of serum serine levels with the risk of overall, digestive system, non-digestive system, and lung cancers (the most common type) were assessed by conditional logistic regression. Results: When serum serine concentration was assessed as quartiles, a significantly higher risk of total cancer (OR = 1.32; 95% CI: 1.01-1.71; P = 0.038) was found in participants in the highest quartile (≥17.68 μg mL-1) compared with participants in the lowest quartile (<13.27 μg mL-1). Similar results were also observed for non-digestive system and lung cancers, but not for digestive system cancers. Significant associations of serum with overall cancer risk were found among all age subgroups, men, non-smokers, non-drinkers, and individuals with lower folic acid levels. Conclusion: High serum serine concentrations were associated with an increased risk of overall, non-digestive system, and lung cancers among Chinese hypertensive adult patients.
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Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China.
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Chenan Liu
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China.
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Mengmeng Song
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China.
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Yaping Wei
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yun Song
- Shenzhen Evergreen Medical Institute, Shenzhen, China.
| | - Ping Chen
- Shenzhen Evergreen Medical Institute, Shenzhen, China.
| | - Lishun Liu
- Shenzhen Evergreen Medical Institute, Shenzhen, China.
| | - Binyan Wang
- Shenzhen Evergreen Medical Institute, Shenzhen, China.
- Institute for Biomedicine, Anhui Medical University, Hefei, China
| | - Hanping Shi
- Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China.
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, China
- Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
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19
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Bui TT, Jang E, Shin JH, Kim TH, Kim H, Choi D, Vu TD, Chung H. Feasibility of Raman spectroscopic identification of gall bladder cancer using extracellular vesicles extracted from bile. Analyst 2023; 148:4156-4165. [PMID: 37501647 DOI: 10.1039/d3an00806a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
Extracellular vesicles (EVs), which are heterogeneous membrane-based vesicles with bilayer cell membrane structures, could be versatile biomarkers for the identification of diverse diseases including cancers. With this potential, this study has attempted the Raman spectroscopic identification of gall bladder (GB) cancer by directly measuring the EV solution extracted from human bile without further sample drying. For this purpose, bile samples were obtained from four normal individuals and 21 GB polyp, eight hepatocellular carcinoma (HCC), and five GB cancer patients, and EVs were extracted from each of the bile samples. The Raman peak shapes of the EVs extracted from the GB cancer samples, especially the relative intensities of peaks in the 1560-1340 cm-1 range, were dissimilar to those of the samples from the normal, GB polyp, and HCC groups. The intensity ratios of peaks at 1537 and 1453 cm-1 and at 1395 and 1359 cm-1 of the GB cancer samples were lower and higher, respectively, than those of the samples of the remaining three groups. The differences of peak intensity ratios were statistically significant based on the Mann-Whitney U test. DNA/RNA bases, amino acids, and bile salts contributed to the spectra of EVs, and their relative abundances seemed to vary according to the occurrence of GB cancer. The varied metabolite compositions and/or structures of EVs were successfully demonstrated by the dissimilar peak intensity ratios in the Raman spectra, thereby enabling the discrimination of GB cancer.
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Affiliation(s)
- Thu Thuy Bui
- Department of Chemistry and Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea.
| | - Eunjin Jang
- Department of Chemistry and Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea.
| | - Ji Hyun Shin
- Department of Surgery, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
| | - Tae Hun Kim
- Department of Surgery, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
| | - Hayoon Kim
- Department of Surgery, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
| | - Dongho Choi
- Department of Surgery, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
| | - Tung Duy Vu
- Faculty of Chemistry, University of Science, Vietnam National University, Hanoi, Vietnam
| | - Hoeil Chung
- Department of Chemistry and Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea.
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20
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Xie Z, Zhu R, Huang X, Yao F, Jin S, Huang Q, Wang D, Li H, Wang Q, Long H, Wu Q. Metabolomic analysis of gut metabolites in patients with colorectal cancer: Association with disease development and outcome. Oncol Lett 2023; 26:358. [PMID: 37545617 PMCID: PMC10398631 DOI: 10.3892/ol.2023.13944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 05/16/2023] [Indexed: 08/08/2023] Open
Abstract
Colorectal cancer (CRC) is one of the leading global malignancies with low 5-year survival and high mortality rates. Despite extensive research, the precise role of gut metabolites in CRC development and clinical outcomes remains unclear, while its elucidation may aid the development of improved clinical diagnosis and treatment options. In the present study, targeted metabolomic analysis was conducted on fecal samples from 35 patients with CRC, 37 patients with colorectal adenoma and 30 healthy controls (HC) to identify metabolite biomarkers. Using orthogonal partial least squares discriminant analysis, metabolomic features distinguishing the three groups were identified. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic utility for distinguishing CRC from HC. The association of gut metabolites with survival in patients with CRC was also analyzed by comparing short-term survivors (STS) and long-term survivors (LTS), and the prognostic ability of metabolites was predicted using Cox regression and Kaplan-Meier analysis. The results of the current study showed that the enriched pathways in CRC included 'caffeine metabolism', 'thiamine metabolism', 'phenylalanine, tyrosine and tryptophan biosynthesis' and 'phenylalanine metabolism'. ROC analysis found that 9,10-dihydroxy-12-octadecenoic acid, cholesterol ester (18:2) and lipoxinA4 distinguished CRC from HC. Joint quantification of these three metabolites resulted in an area under the ROC curve of 0.969 in the diagnosis of CRC. The analysis of the current study also showed that the expression of metabolites involved in 'sphingolipid metabolism' was mainly dysregulated in LTS and STS, while N-acetylmannosamine and 2,5-dihydroxybenzaldehyde were associated with better overall survival. In conclusion, the present study provided preliminary insight into the metabolic changes associated with CRC and may have important implications for the development of future diagnostic and treatment strategies.
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Affiliation(s)
- Zhufu Xie
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Rui Zhu
- Department of Gastroenterology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
| | - Xiaoying Huang
- Department of Public Health, The First Hospital of Wuhan, Wuhan, Hubei 430000, P.R. China
| | - Fei Yao
- College of Medical Science, China Three Gorges University, Yichang, Hubei 443002, P.R. China
| | - Shu Jin
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Qiyou Huang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Dequan Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Huan Li
- Department of Gastroenterology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Hui Long
- Department of Gastroenterology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
| | - Qingming Wu
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
- Department of Gastroenterology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
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21
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Bhatt K, Orlando T, Meuwis MA, Louis E, Stefanuto PH, Focant JF. Comprehensive Insight into Colorectal Cancer Metabolites and Lipids for Human Serum: A Proof-of-Concept Study. Int J Mol Sci 2023; 24:ijms24119614. [PMID: 37298566 DOI: 10.3390/ijms24119614] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 μL serum) and metabolomics (50 μL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.
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Affiliation(s)
- Kinjal Bhatt
- Organic and Biological Analytical Chemistry Group (OBiAChem), MolSys, University of Liège, 4000 Liège, Belgium
| | - Titziana Orlando
- Organic and Biological Analytical Chemistry Group (OBiAChem), MolSys, University of Liège, 4000 Liège, Belgium
| | - Marie-Alice Meuwis
- GIGA Institute, Translational Gastroenterology and CHU de Liège, Hepato-Gastroenterology and Digestive Oncology, Quartier Hôpital, University of Liège, Avenue de l'Hôpital 13, B34-35, 4000 Liège, Belgium
| | - Edouard Louis
- GIGA Institute, Translational Gastroenterology and CHU de Liège, Hepato-Gastroenterology and Digestive Oncology, Quartier Hôpital, University of Liège, Avenue de l'Hôpital 13, B34-35, 4000 Liège, Belgium
| | - Pierre-Hugues Stefanuto
- Organic and Biological Analytical Chemistry Group (OBiAChem), MolSys, University of Liège, 4000 Liège, Belgium
| | - Jean-François Focant
- Organic and Biological Analytical Chemistry Group (OBiAChem), MolSys, University of Liège, 4000 Liège, Belgium
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22
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Rothwell JA, Bešević J, Dimou N, Breeur M, Murphy N, Jenab M, Wedekind R, Viallon V, Ferrari P, Achaintre D, Gicquiau A, Rinaldi S, Scalbert A, Huybrechts I, Prehn C, Adamski J, Cross AJ, Keun H, Chadeau-Hyam M, Boutron-Ruault MC, Overvad K, Dahm CC, Nøst TH, Sandanger TM, Skeie G, Zamora-Ros R, Tsilidis KK, Eichelmann F, Schulze MB, van Guelpen B, Vidman L, Sánchez MJ, Amiano P, Ardanaz E, Smith-Byrne K, Travis R, Katzke V, Kaaks R, Derksen JWG, Colorado-Yohar S, Tumino R, Bueno-de-Mesquita B, Vineis P, Palli D, Pasanisi F, Eriksen AK, Tjønneland A, Severi G, Gunter MJ. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts. BMC Med 2023; 21:80. [PMID: 36855092 PMCID: PMC9976469 DOI: 10.1186/s12916-023-02739-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/16/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. RESULTS Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. CONCLUSIONS Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
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Affiliation(s)
- Joseph A Rothwell
- Centre for Epidemiology and Population Health (Inserm U1018), Exposome and Heredity team, Faculté de Médecine, Université Paris-Saclay, UVSQ, Gustave Roussy, F-94805, Villejuif, France.
| | - Jelena Bešević
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Niki Dimou
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Marie Breeur
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Neil Murphy
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Roland Wedekind
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Vivian Viallon
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Pietro Ferrari
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - David Achaintre
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Audrey Gicquiau
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Sabina Rinaldi
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Augustin Scalbert
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Inge Huybrechts
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Cornelia Prehn
- Metabolomics and Proteomics Core, Helmholtz Zentrum München, 85764, Neuherberg, Germany
| | - Jerzy Adamski
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117597, Singapore
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
- Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
| | - Amanda J Cross
- School of Public Health, Imperial College London, London, UK
| | - Hector Keun
- Department of Surgery & Cancer, Imperial College London, London, UK
| | | | - Marie-Christine Boutron-Ruault
- Centre for Epidemiology and Population Health (Inserm U1018), Exposome and Heredity team, Faculté de Médecine, Université Paris-Saclay, UVSQ, Gustave Roussy, F-94805, Villejuif, France
| | - Kim Overvad
- Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000, Aarhus, Denmark
| | - Christina C Dahm
- Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000, Aarhus, Denmark
| | - Therese Haugdahl Nøst
- Faculty of Health Sciences, Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Torkjel M Sandanger
- Faculty of Health Sciences, Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Guri Skeie
- Faculty of Health Sciences, Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Raul Zamora-Ros
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Kostas K Tsilidis
- School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Fabian Eichelmann
- German Center for Diabetes Research (DZD), Munchen-Neuherberg, Germany
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
| | - Bethany van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Linda Vidman
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Maria-José Sánchez
- Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain
- Instituto de Investigación Biosanitaria ibs. GRANADA, 18012, Granada, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain
| | - Pilar Amiano
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain
- Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain
- Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
| | - Eva Ardanaz
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Navarra Public Health Institute, Leyre 15, 31003, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Karl Smith-Byrne
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
| | - Ruth Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Verena Katzke
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
| | - Rudolf Kaaks
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
| | - Jeroen W G Derksen
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Sandra Colorado-Yohar
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy
| | - Bas Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720, BA, Bilthoven, The Netherlands
| | - Paolo Vineis
- School of Public Health, Imperial College London, London, UK
- Italian Institute of Technology, Genova, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Fabrizio Pasanisi
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Anne Kirstine Eriksen
- Danish Cancer Society Research Center, Diet, Genes and Environment, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Diet, Genes and Environment, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
| | - Gianluca Severi
- Centre for Epidemiology and Population Health (Inserm U1018), Exposome and Heredity team, Faculté de Médecine, Université Paris-Saclay, UVSQ, Gustave Roussy, F-94805, Villejuif, France
- Department of Statistics, Computer Science, Applications "G. Parenti" University of Florence, Florence, Italy
| | - Marc J Gunter
- International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008, Lyon, France
- School of Public Health, Imperial College London, London, UK
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Costantini S, Di Gennaro E, Capone F, De Stefano A, Nasti G, Vitagliano C, Setola SV, Tatangelo F, Delrio P, Izzo F, Avallone A, Budillon A. Plasma metabolomics, lipidomics and cytokinomics profiling predict disease recurrence in metastatic colorectal cancer patients undergoing liver resection. Front Oncol 2023; 12:1110104. [PMID: 36713567 PMCID: PMC9875807 DOI: 10.3389/fonc.2022.1110104] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 12/22/2022] [Indexed: 01/13/2023] Open
Abstract
Purpose In metastatic colorectal cancer (mCRC) patients (pts), treatment strategies integrating liver resection with induction chemotherapy offer better 5-year survival rates than chemotherapy alone. However, liver resection is a complex and costly procedure, and recurrence occurs in almost 2/3rds of pts, suggesting the need to identify those at higher risk. The aim of this work was to evaluate whether the integration of plasma metabolomics and lipidomics combined with the multiplex analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery, beyond or in combination with clinical morphovolumetric criteria. Experimental design Peripheral blood metabolomics and lipidomics were performed by 600 MHz NMR spectroscopy on plasma from 30 unresectable mCRC pts treated with bevacizumab plus oxaliplatin-based regimens within the Obelics trial (NCT01718873) and subdivided into responder (R) and non-R (NR) according to 1-year disease-free survival (DFS): ≥ 1-year (R, n = 12) and < 1-year (NR, n = 18). A large panel of cytokines, chemokines, and growth factors was evaluated on the same plasma using Luminex xMAP-based multiplex bead-based immunoassay technology. A multiple biomarkers model was built using a support vector machine (SVM) classifier. Results Sparse partial least squares discriminant analysis (sPLS-DA) and loading plots obtained by analyzing metabolomics profiles of samples collected at the time of response evaluation when resectability was established showed significantly different levels of metabolites between the two groups. Two metabolites, 3-hydroxybutyrate and histidine, significantly predicted DFS and overall survival. Lipidomics analysis confirmed clear differences between the R and NR pts, indicating a statistically significant increase in lipids (cholesterol, triglycerides and phospholipids) in NR pts, reflecting a nonspecific inflammatory response. Indeed, a significant increase in proinflammatory cytokines was demonstrated in NR pts plasma. Finally, a multiple biomarkers model based on the combination of presurgery plasma levels of 3-hydroxybutyrate, cholesterol, phospholipids, triglycerides and IL-6 was able to correctly classify patients by their DFS with good accuracy. Conclusion Overall, this exploratory study suggests the potential of these combined biomarker approaches to predict outcomes in mCRC patients who are candidates for liver metastasis resection after induction treatment for defining personalized management and treatment strategies.
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Affiliation(s)
- Susan Costantini
- Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Elena Di Gennaro
- Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Francesca Capone
- Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Alfonso De Stefano
- Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Guglielmo Nasti
- Innovative Therapy for Abdominal Metastases Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Carlo Vitagliano
- Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Sergio Venanzio Setola
- Radiology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Fabiana Tatangelo
- Pathology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Paolo Delrio
- Colorectal Oncological Surgery Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Francesco Izzo
- Hepatobiliary Surgery Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Antonio Avallone
- Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy
| | - Alfredo Budillon
- Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy,*Correspondence: Alfredo Budillon,
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Guo J, Pan Y, Chen J, Jin P, Tang S, Wang H, Su H, Wang Q, Chen C, Xiong F, Liu K, Li Y, Su M, Tang T, He Y, Sheng J. Serum metabolite signatures in normal individuals and patients with colorectal adenoma or colorectal cancer using UPLC-MS/MS method. J Proteomics 2023; 270:104741. [PMID: 36174955 DOI: 10.1016/j.jprot.2022.104741] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/19/2022] [Accepted: 09/06/2022] [Indexed: 02/01/2023]
Abstract
Colorectal cancer (CRC) is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenoma to adenocarcinoma, which provides a long screening window for clinical detection. However, early diagnosis of sporadic colorectal adenoma (CRA) and CRC using serum metabolic screening remains unclear. The purpose of this study was to identify some promising signatures for distinguishing the different pathological metabolites of colorectal mucosal malignant transformation. A total of 238 endogenous metabolites were elected. We found that CRA and CRC patients had 72 and 73 different metabolites compared with healthy controls, respectively. There were 20 different metabolites between CRA and CRC patients. The potential metabolites of tumor growth (including patients with CRA and CRC) were found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, Sarcosine, TXB 2, 12-Hete, and chenodeoxycholic acid. Compared with CRA, 3,4,5-trimethoxybenzoic acid was significantly higher in CRC patients. There results prompt us to use the potential serum signatures to screen CRC as the novel strategy. Serum metabolite screening is useful for early detection of mucosal intestinal malignancy. We will further investigate the roles of these promising biomarkers during intestinal tumorigenesis in future. SIGNIFICANCE: CRC is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenomas to adenocarcinoma, which provides a long screening window for about 5-10 years. We adopt the metabolic analysis of extensive targeted metabolic technology. The main purpose of the metabolic group analysis is to detect and screen the different metabolites, thereby performing related functional prediction and analysis of the differential metabolites. In our study, 30 samples are selected, divided into 3 groups for metabolic analysis, and 238 metabolites are elected. In 238 metabolites, we find that CRA patients have 72 different metabolites compared with health control. Compared with health control, CRC have 73 different metabolites. Compared with CRA and CRC patients, there are 20 different metabolites. The annotation results of the significantly different metabolites are classified according to the KEGG pathway type. The potential metabolites of tumor growth stage (including patients with CRA and CRC) are found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, sarcosine, TXB 2, 12-Hete and chenodeoxycholic acid. Compared with CRA patients, CRC patients had significantly higher 3,4,5-trimethoxybenzoic acid level. It is prompted to use serum different metabolites to screen CRC to provide new possibilities.
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Affiliation(s)
- Jiachi Guo
- Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China
| | - Yuanming Pan
- Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, No. 9 Beiguan Street, Tongzhou District, Beijing 101149, China
| | - Jigui Chen
- Department of Colorectal and Anal Surgery Wuhan, No. 8 Hospital. No. 1307 Zhongshan Avenue, Jiang'an District, Hankou, Wuhan City, Hubei 430010, China
| | - Peng Jin
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China
| | - Shan Tang
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China
| | - Haihong Wang
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China
| | - Hui Su
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China
| | - Qian Wang
- Department of Colorectal and Anal Surgery Wuhan, No. 8 Hospital. No. 1307 Zhongshan Avenue, Jiang'an District, Hankou, Wuhan City, Hubei 430010, China
| | - Chao Chen
- Department of Colorectal and Anal Surgery Wuhan, No. 8 Hospital. No. 1307 Zhongshan Avenue, Jiang'an District, Hankou, Wuhan City, Hubei 430010, China
| | - Fei Xiong
- Department of Colorectal and Anal Surgery Wuhan, No. 8 Hospital. No. 1307 Zhongshan Avenue, Jiang'an District, Hankou, Wuhan City, Hubei 430010, China
| | - Kejia Liu
- DHC Mediway Technology Co., Ltd., 14F, Zijin Digital Park, Zhongguancun, Haidian District, Beijing 100190, China
| | - Yansheng Li
- DHC Mediway Technology Co., Ltd., 14F, Zijin Digital Park, Zhongguancun, Haidian District, Beijing 100190, China
| | - Mingliang Su
- DHC Mediway Technology Co., Ltd., 14F, Zijin Digital Park, Zhongguancun, Haidian District, Beijing 100190, China
| | - Tang Tang
- Wuhan Metwell Biotechnology Co., Ltd., Building B7/B8, Biological Industry Innovation Base, 666 Gaoxin Avenue, Donghu New Technology Development Zone, Wuhan City, Hubei 430075, China
| | - Yuqi He
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China; The Second School of Clinical Medicine, Southern Medical University, 253 Middle Industrial Avenue, Guangzhou City, Guangdong 510280, China; Department of Gastroenterology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, No. 9 Beiguan Street, Tongzhou District, Beijing 101149, China.
| | - Jianqiu Sheng
- Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28, Fuxing Road Haidian District, Beijing 100853, China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China.
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Savva KV, Das B, Antonowicz S, Hanna GB, Peters CJ. Progress with Metabolomic Blood Tests for Gastrointestinal Cancer Diagnosis-An Assessment of Biomarker Translation. Cancer Epidemiol Biomarkers Prev 2022; 31:2095-2105. [PMID: 36215181 DOI: 10.1158/1055-9965.epi-22-0307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/27/2022] [Accepted: 09/30/2022] [Indexed: 12/30/2022] Open
Abstract
There is an urgent need for cost-effective, non-invasive tools to detect early stages of gastrointestinal cancer (colorectal, gastric, and esophageal cancers). Despite many publications suggesting circulating metabolites acting as accurate cancer biomarkers, few have reached the clinic. In upper gastrointestinal cancer this is critically important, as there is no test to complement gold-standard endoscopic evaluation in patients with mild symptoms that do not meet referral criteria. Therefore, this study aimed to describe and solve this translational gap. Studies reporting diagnostic accuracy of metabolomic blood-based gastrointestinal cancer biomarkers from 2007 to 2020 were systematically reviewed and progress of each biomarker along the discovery-validation-adoption pathway was mapped. Successful biomarker translation was defined as a composite endpoint, including patent protection/FDA approval/recommendation in national guidelines. The review found 77 biomarker panels of gastrointestinal cancer, including 25 with an AUROC >0.9. All but one was stalled at the discovery phase, 9.09% were patented and none were clinically approved, confirming the extent of biomarker translational gap. In addition, there were numerous "re-discoveries," including histidine, discovered in 7 colorectal studies. Finally, this study quantitatively supports the presence of a translational gap between discovery and clinical adoption, despite clear evidence of highly performing biomarkers with significant potential clinical value.
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Affiliation(s)
- Katerina-Vanessa Savva
- Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, London, United Kingdom
| | - Bibek Das
- Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, London, United Kingdom
| | - Stefan Antonowicz
- Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, London, United Kingdom
| | - George B Hanna
- Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, London, United Kingdom
| | - Christopher J Peters
- Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, London, United Kingdom
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Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives. Cancers (Basel) 2022; 14:cancers14225545. [PMID: 36428637 PMCID: PMC9688479 DOI: 10.3390/cancers14225545] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/15/2022] Open
Abstract
Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.
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Yu QQ, Zhang H, Zhao S, Xie D, Zhao H, Chen W, Pang M, Han B, Jiang P. Systematic evaluation of irinotecan-induced intestinal mucositis based on metabolomics analysis. Front Pharmacol 2022; 13:958882. [PMID: 36188576 PMCID: PMC9520243 DOI: 10.3389/fphar.2022.958882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of chemotherapy, especially in regimens containing irinotecan (CPT-11). Several studies on the pathologic mechanisms of CIM focused on both the genomics and molecular pathways triggered by chemotherapy. However, systematic evaluation of metabolomic analysis in irinotecan-induced intestinal mucositis (IIM) has not been investigated. This study aimed to comprehensively analyze metabolite changes in main tissues of IIM mouse models. Male ICR mice were assigned to two groups: the model group (n = 11) treated with CPT-11 (20 mg/kg daily; i.p.) and the control group (n= 11) with solvent for 9 days. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the metabolic alterations in the serum, intestinal, colonic, hepatic, and splenic samples of mice between two groups by multivariate statistical analyses, including GC–MS data processing, pattern recognition analysis, and pathway analysis. Forty-six metabolites, including hydrocarbons, amino acids, lipids, benzenoids, hydroxy acids, and amines, had significant changes in levels in tissues and sera of IIM mouse models. The most important pathways related to the identified metabolites were the glycerolipid metabolism in the colon and aminoacyl-tRNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism in the liver. Our study firstly provided a comprehensive and systematic view of metabolic alterations of IIM using GC-MS analysis. The characterizations of metabolic changes could offer profound and theoretical insight into exploring new biomarkers for diagnosis and treatment of IIM.
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Affiliation(s)
- Qing-Qing Yu
- Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao, China
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Heng Zhang
- Department of Laboratory, Shandong Daizhuang Hospital, Jining, China
| | - Shiyuan Zhao
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Dadi Xie
- Department of Endocrine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Haibo Zhao
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Weidong Chen
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Min Pang
- MNR Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, China
| | - Baoqin Han
- Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
- *Correspondence: Baoqin Han, ; Pei Jiang,
| | - Pei Jiang
- Jining First People’s Hospital, Jining Medical College, Jining, China
- *Correspondence: Baoqin Han, ; Pei Jiang,
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He Q, Zhang N, Liang Q, Wang Z, Chen P, Song Y, Zhou Z, Wei Y, Duan Y, Wang B, Qin P, Qin X, Xu X. Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT). Front Nutr 2022; 9:946277. [PMID: 35903445 PMCID: PMC9315370 DOI: 10.3389/fnut.2022.946277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
Background Serine plays a key role in numerous cellular processes, the levels and metabolism is therefore of critical importance. However, few data are available to illustrate the association of serine with long-term health effects, especially, the predictive value for long-term mortality. Objective This study was conducted to evaluate the relationship between serum serine levels and all-cause mortality in general hypertensive patients in a longitudinal cohort, and to examine the potential effect modifiers. Methods A nested case-control (NCC) study was conducted utilizing 20702 hypertensive participants from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, actively controlled trial conducted from May 2008 to August 2013 in China. The current study included 291 cases of all-cause mortality and 291 controls matched on age (≤ 1 year), sex and treatment group. All-cause mortality was the main outcome in this analysis, which included death due to any reason. Results With the increase in serum serine levels, the risk of all-cause mortality first increased before flattening. After adjusting for related variables, the risk of mortality increased significantly with the increase of serum serine levels. Compared with group Q1, the mortality risk of group Q2, Q3 and Q4 were significantly increased [ORs, 95% CI: Q2: 2.32, (1.32–4.07); Q3: 2.59, (1.48–4.54); and Q4: 1.85, (1.07–3.22)]. In the exploratory analysis, we observed three effect modifiers, total homocysteine, 5-Methyltetrahydrofolate, and estimated glomerular filtration rate significantly modified the serum serine and all-cause mortality association. Conclusion Serum serine levels were significantly associated with an increased risk of all-cause mortality in hypertensive patients. Our results and findings, if confirmed further, suggest that serum serine should be considered as a marker for screening risk factors of mortality. Clinical Trial Registration [https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.], identifier [CSPPT, NCT00794885].
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Affiliation(s)
- Qiangqiang He
- Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Nan Zhang
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Qiongyue Liang
- State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Zhuo Wang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Ping Chen
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Yun Song
- AUSA Research Institute, Shenzhen AUSA Pharmed Co. Ltd., Shenzhen, China
- Institute of Biomedicine, Anhui Medical University, Hefei, China
| | - Ziyi Zhou
- Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
- Shenzhen Evergreen Medical Institute, Shenzhen, China
| | - Yaping Wei
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yong Duan
- Yunnan Key Laboratory of Laboratory Medicine, Kunming, China
- Department of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Binyan Wang
- Shenzhen Evergreen Medical Institute, Shenzhen, China
- National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Peiwu Qin
- Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China
| | - Xianhui Qin
- National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiping Xu
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China
- National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence: Xiping Xu
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Luu HN, Paragomi P, Wang R, Huang JY, Adams-Haduch J, Midttun Ø, Ulvik A, Nguyen TC, Brand RE, Gao Y, Ueland PM, Yuan JM. The Association between Serum Serine and Glycine and Related-Metabolites with Pancreatic Cancer in a Prospective Cohort Study. Cancers (Basel) 2022; 14:2199. [PMID: 35565328 PMCID: PMC9105477 DOI: 10.3390/cancers14092199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/18/2022] [Accepted: 04/25/2022] [Indexed: 12/24/2022] Open
Abstract
Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14−0.75) and 0.25 (0.11−0.58), respectively, compared with their respective lowest quartiles (both p’s < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention.
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Affiliation(s)
- Hung N. Luu
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 130 De Soto St, Pittsburgh, PA 15261, USA
| | - Pedram Paragomi
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
| | - Renwei Wang
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
| | - Joyce Y. Huang
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 130 De Soto St, Pittsburgh, PA 15261, USA
| | - Jennifer Adams-Haduch
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
| | - Øivind Midttun
- Bevital A/S, Jonas Lies Veg 87, 5021 Bergen, Norway; (Ø.M.); (P.M.U.)
| | - Arve Ulvik
- Department of Clinical Science, University of Bergen, Postboks 7804, 5020 Bergen, Norway;
| | - Tin C. Nguyen
- Department of Computer Science and Engineering, University of Nevada at Reno, Reno, NV 89557, USA;
| | - Randall E. Brand
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Yutang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201112, China;
| | - Per Magne Ueland
- Bevital A/S, Jonas Lies Veg 87, 5021 Bergen, Norway; (Ø.M.); (P.M.U.)
- Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway
| | - Jian-Min Yuan
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, 5150 Centre Avenue, Suite 4C, Pittsburgh, PA 15232, USA; (P.P.); (R.W.); (J.Y.H.); (J.A.-H.); (R.E.B.); (J.-M.Y.)
- Department of Epidemiology, School of Public Health, University of Pittsburgh, 130 De Soto St, Pittsburgh, PA 15261, USA
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Distinct Urinary Metabolic Biomarkers of Human Colorectal Cancer. DISEASE MARKERS 2022; 2022:1758113. [PMID: 35521635 PMCID: PMC9064491 DOI: 10.1155/2022/1758113] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/26/2022] [Accepted: 03/08/2022] [Indexed: 11/30/2022]
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality rate due to its poor diagnosis in the early stage. Here, we report a urinary metabolomic study on a cohort of CRC patients (n =67) and healthy controls (n =21) using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Pathway analysis showed that a series of pathways that belong to amino acid metabolism, carbohydrate metabolism, and lipid metabolism were dysregulated, for instance the glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glycolysis, and TCA cycle. A total of 48 differential metabolites were identified in CRC compared to controls. A panel of 12 biomarkers composed of chenodeoxycholic acid, vanillic acid, adenosine monophosphate, glycolic acid, histidine, azelaic acid, hydroxypropionic acid, glycine, 3,4-dihydroxymandelic acid, 4-hydroxybenzoic acid, oxoglutaric acid, and homocitrulline were identified by Random Forest (RF), Support Vector Machine (SVM), and Boruta analysis classification model and validated by Gradient Boosting (GB), Logistic Regression (LR), and Random Forest diagnostic model, which were able to discriminate CRC subjects from healthy controls. These urinary metabolic biomarkers provided a novel and promising molecular approach for the early diagnosis of CRC.
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Larkin JR, Anthony S, Johanssen VA, Yeo T, Sealey M, Yates AG, Smith CF, Claridge TD, Nicholson BD, Moreland JA, Gleeson F, Sibson NR, Anthony DC, Probert F. Metabolomic Biomarkers in Blood Samples Identify Cancers in a Mixed Population of Patients with Nonspecific Symptoms. Clin Cancer Res 2022; 28:1651-1661. [PMID: 34983789 PMCID: PMC7613224 DOI: 10.1158/1078-0432.ccr-21-2855] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/08/2021] [Accepted: 11/16/2021] [Indexed: 11/16/2022]
Abstract
PURPOSE Early diagnosis of cancer is critical for improving patient outcomes, but cancers may be hard to diagnose if patients present with nonspecific signs and symptoms. We have previously shown that nuclear magnetic resonance (NMR) metabolomics analysis can detect cancer in animal models and distinguish between differing metastatic disease burdens. Here, we hypothesized that biomarkers within the blood metabolome could identify cancers within a mixed population of patients referred from primary care with nonspecific symptoms, the so-called "low-risk, but not no-risk" patient group, as well as distinguishing between those with and without metastatic disease. EXPERIMENTAL DESIGN Patients (n = 304 comprising modeling, n = 192, and test, n = 92) were recruited from 2017 to 2018 from the Oxfordshire Suspected CANcer (SCAN) pathway, a multidisciplinary diagnostic center (MDC) referral pathway for patients with nonspecific signs and symptoms. Blood was collected and analyzed by NMR metabolomics. Orthogonal partial least squares discriminatory analysis (OPLS-DA) models separated patients, based upon diagnoses received from the MDC assessment, within 62 days of initial appointment. RESULTS Area under the ROC curve for identifying patients with solid tumors in the independent test set was 0.83 [95% confidence interval (CI): 0.72-0.95]. Maximum sensitivity and specificity were 94% (95% CI: 73-99) and 82% (95% CI: 75-87), respectively. We could also identify patients with metastatic disease in the cohort of patients with cancer with sensitivity and specificity of 94% (95% CI: 72-99) and 88% (95% CI: 53-98), respectively. CONCLUSIONS For a mixed group of patients referred from primary care with nonspecific signs and symptoms, NMR-based metabolomics can assist their diagnosis, and may differentiate both those with malignancies and those with and without metastatic disease. See related commentary by Van Tine and Lyssiotis, p. 1477.
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Affiliation(s)
- James R. Larkin
- Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom
| | - Susan Anthony
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Vanessa A. Johanssen
- Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom
| | - Tianrong Yeo
- Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- Department of Neurology, National Neuroscience Institute, Singapore
- Duke-NUS Medical School, Singapore
| | - Megan Sealey
- Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Abi G. Yates
- Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Claire Friedemann Smith
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
| | | | - Brian D. Nicholson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
| | - Julie-Ann Moreland
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Fergus Gleeson
- Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Nicola R. Sibson
- Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom
| | - Daniel C. Anthony
- Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Fay Probert
- Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- Department of Chemistry, University of Oxford, Oxford, United Kingdom
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Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Martinez-Bernabe T, Sastre-Serra J, Roca P, Pons DG, Oliver J, Reyes J. Use of Omics Technologies for the Detection of Colorectal Cancer Biomarkers. Cancers (Basel) 2022; 14:817. [PMID: 35159084 PMCID: PMC8834235 DOI: 10.3390/cancers14030817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.
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Affiliation(s)
- Marina Alorda-Clara
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Margalida Torrens-Mas
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Translational Research in Aging and Longevity (TRIAL) Group, Instituto de Investigación Sanitaria Illes Balears (IdISBa), E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Pere Miquel Morla-Barcelo
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
| | - Toni Martinez-Bernabe
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Jorge Sastre-Serra
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Pilar Roca
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Daniel Gabriel Pons
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Jordi Oliver
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Jose Reyes
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Servicio Aparato Digestivo, Hospital Comarcal de Inca, E-07300 Inca, Illes Balears, Spain
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The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review. Cancers (Basel) 2022; 14:cancers14030725. [PMID: 35158992 PMCID: PMC8833341 DOI: 10.3390/cancers14030725] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/16/2022] [Accepted: 01/25/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Colorectal Cancer (CRC) is one of the leading causes of cancer-related death in the United States. Current diagnosis techniques are either highly invasive or lack sensitivity, suggesting the need for alternative techniques for biomarker detection. Metabolomics represents one such technique with great promise in identifying CRC biomarkers with high sensitivity and specificity, but thus far is rarely employed in a clinical setting. In order to provide a framework for future clinical usage, we characterized dysregulated metabolites across recent literature, identifying metabolites dysregulated across a variety of biospecimens. We additionally put special focus on the interplay of the gut microbiome and perturbed metabolites in CRC. We were able to identify many metabolites showing consistent dysregulation in CRC, demonstrating the value of metabolomics as a promising diagnostic technique. Abstract Colorectal cancer (CRC) is a highly prevalent disease with poor prognostic outcomes if not diagnosed in early stages. Current diagnosis techniques are either highly invasive or lack sufficient sensitivity. Thus, identifying diagnostic biomarkers of CRC with high sensitivity and specificity is desirable. Metabolomics represents an analytical profiling technique with great promise in identifying such biomarkers and typically represents a close tie with the phenotype of a specific disease. We thus conducted a systematic review of studies reported from January 2012 to July 2021 relating to the detection of CRC biomarkers through metabolomics to provide a collection of knowledge for future diagnostic development. We identified thirty-seven metabolomics studies characterizing CRC, many of which provided metabolites/metabolic profile-based diagnostic models with high sensitivity and specificity. These studies demonstrated that a great number of metabolites can be differentially regulated in CRC patients compared to healthy controls, adenomatous polyps, or across stages of CRC. Among these metabolite biomarkers, especially dysregulated were certain amino acids, fatty acids, and lysophosphatidylcholines. Additionally, we discussed the contribution of the gut bacterial population to pathogenesis of CRC through their modulation to fecal metabolite pools and summarized the established links in the literature between certain microbial genera and altered metabolite levels in CRC patients. Taken together, we conclude that metabolomics presents itself as a promising and effective method of CRC biomarker detection.
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Tevini J, Eder SK, Huber-Schönauer U, Niederseer D, Strebinger G, Gostner JM, Aigner E, Datz C, Felder TK. Changing Metabolic Patterns along the Colorectal Adenoma–Carcinoma Sequence. J Clin Med 2022; 11:jcm11030721. [PMID: 35160173 PMCID: PMC8836789 DOI: 10.3390/jcm11030721] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity and specificity of colonoscopy in combination with histopathological examination. The present study identifies serum metabolite patterns of treatment-naïve patients, diagnosed with either advanced adenoma (AA) or CRC in colonoscopy screenings, in the framework of the SAKKOPI (Salzburg Colon Cancer Prevention Initiative) program. We used a targeted flow injection analysis and liquid chromatography-tandem mass spectrometry metabolomics approach (FIA- and LC-MS/MS) to characterise the serum metabolomes of an initial screening cohort and two validation cohorts (in total 66 CRC, 76 AA and 93 controls). The lipidome was significantly perturbed, with a proportion of lipid species being downregulated in CRC patients, as compared to AA and controls. The predominant alterations observed were in the levels of lyso-lipids, glycerophosphocholines and acylcarnitines, but additionally, variations in the quantity of hydroxylated sphingolipids could be detected. Changed amino acid metabolism was restricted mainly to metabolites of the arginine/dimethylarginine/NO synthase pathway. The identified metabolic divergences observed in CRC set the foundation for mechanistic studies to characterise biochemical pathways that become deregulated during progression through the adenoma to carcinoma sequence and highlight the key importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies.
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Affiliation(s)
- Julia Tevini
- Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
| | - Sebastian K. Eder
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria; (S.K.E.); (E.A.)
- Department of Pediatrics and Adolescent Medicine, St. Anna Children’s Hospital, Medical University of Vienna, 1090 Vienna, Austria
| | - Ursula Huber-Schönauer
- Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, Austria; (U.H.-S.); (G.S.)
| | - David Niederseer
- Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland;
| | - Georg Strebinger
- Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, Austria; (U.H.-S.); (G.S.)
| | - Johanna M. Gostner
- Institute of Medical Biochemistry, Innsbruck Medical University, 6020 Innsbruck, Austria;
| | - Elmar Aigner
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria; (S.K.E.); (E.A.)
| | - Christian Datz
- Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, Austria; (U.H.-S.); (G.S.)
- Correspondence: (C.D.); (T.K.F.); Tel.: +43-5-7255-58126 (T.K.F.)
| | - Thomas K. Felder
- Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
- Correspondence: (C.D.); (T.K.F.); Tel.: +43-5-7255-58126 (T.K.F.)
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Troisi J, Tafuro M, Lombardi M, Scala G, Richards SM, Symes SJK, Ascierto PA, Delrio P, Tatangelo F, Buonerba C, Pierri B, Cerino P. A Metabolomics-Based Screening Proposal for Colorectal Cancer. Metabolites 2022; 12:metabo12020110. [PMID: 35208185 PMCID: PMC8878838 DOI: 10.3390/metabo12020110] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/17/2022] [Accepted: 01/22/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.
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Affiliation(s)
- Jacopo Troisi
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
- Theoreo srl, Via degli Ulivi 3, 84090 Montecorvino Pugliano, Italy; (M.L.); (G.S.)
- Correspondence: or (J.T.); (B.P.)
| | - Maria Tafuro
- Centro di Referenza Nazionale per l’Analisi e Studio di Correlazione tra Ambiente, Animale e Uomo, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy; (M.T.); (C.B.); (P.C.)
| | - Martina Lombardi
- Theoreo srl, Via degli Ulivi 3, 84090 Montecorvino Pugliano, Italy; (M.L.); (G.S.)
| | - Giovanni Scala
- Theoreo srl, Via degli Ulivi 3, 84090 Montecorvino Pugliano, Italy; (M.L.); (G.S.)
- Hosmotic srl, Via R. Bosco 178, 80069 Vico Equense, Italy
| | - Sean M. Richards
- Department of Obstetrics and Gynecology, Section on Maternal-Fetal Medicine, University of Tennessee College of Medicine, 960 East Third Street, Suite 100, 902 McCallie Avenue, Chattanooga, TN 37403, USA; (S.M.R.); (S.J.K.S.)
- Department of Biology, Geology and Environmental Sciences, University of Tennessee at Chattanooga, 615 McCallie Ave., Chattanooga, TN 37403, USA
| | - Steven J. K. Symes
- Department of Obstetrics and Gynecology, Section on Maternal-Fetal Medicine, University of Tennessee College of Medicine, 960 East Third Street, Suite 100, 902 McCallie Avenue, Chattanooga, TN 37403, USA; (S.M.R.); (S.J.K.S.)
- Department of Chemistry and Physics, University of Tennessee at Chattanooga, 615 McCallie Ave., Chattanooga, TN 37403, USA
| | - Paolo Antonio Ascierto
- Istituto Nazionale Tumori Fondazione Pascale IRCCS, 80131 Napoli, Italy; (P.A.A.); (P.D.); (F.T.)
| | - Paolo Delrio
- Istituto Nazionale Tumori Fondazione Pascale IRCCS, 80131 Napoli, Italy; (P.A.A.); (P.D.); (F.T.)
| | - Fabiana Tatangelo
- Istituto Nazionale Tumori Fondazione Pascale IRCCS, 80131 Napoli, Italy; (P.A.A.); (P.D.); (F.T.)
| | - Carlo Buonerba
- Centro di Referenza Nazionale per l’Analisi e Studio di Correlazione tra Ambiente, Animale e Uomo, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy; (M.T.); (C.B.); (P.C.)
| | - Biancamaria Pierri
- Centro di Referenza Nazionale per l’Analisi e Studio di Correlazione tra Ambiente, Animale e Uomo, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy; (M.T.); (C.B.); (P.C.)
- Correspondence: or (J.T.); (B.P.)
| | - Pellegrino Cerino
- Centro di Referenza Nazionale per l’Analisi e Studio di Correlazione tra Ambiente, Animale e Uomo, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy; (M.T.); (C.B.); (P.C.)
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Salmerón AM, Tristán AI, Abreu AC, Fernández I. Serum Colorectal Cancer Biomarkers Unraveled by NMR Metabolomics: Past, Present, and Future. Anal Chem 2022; 94:417-430. [PMID: 34806875 PMCID: PMC8756394 DOI: 10.1021/acs.analchem.1c04360] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Ana M. Salmerón
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ana I. Tristán
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ana C. Abreu
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
| | - Ignacio Fernández
- Department of Chemistry and
Physics, Research Centre CIAIMBITAL, University
of Almería, Ctra. Sacramento, s/n, 04120 Almería, Spain
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Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer. DISEASE MARKERS 2021; 2021:6858809. [PMID: 34917201 PMCID: PMC8670981 DOI: 10.1155/2021/6858809] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/13/2021] [Accepted: 11/18/2021] [Indexed: 12/21/2022]
Abstract
Background The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. Methods A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. Results In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. Conclusion The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.
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He X, Gu J, Zou D, Yang H, Zhang Y, Ding Y, Teng L. NMR-Based Metabolomics Analysis Predicts Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer. Front Mol Biosci 2021; 8:708052. [PMID: 34796199 PMCID: PMC8592909 DOI: 10.3389/fmolb.2021.708052] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 09/10/2021] [Indexed: 12/17/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is the most fatal type of breast cancer (BC). Due to the lack of relevant targeted drug therapy, in addition to surgery, chemotherapy is still the most common treatment option for TNBC. TNBC is heterogeneous, and different patients have an unusual sensitivity to chemotherapy. Only part of the patients will benefit from chemotherapy, so neoadjuvant chemotherapy (NAC) is controversial in the treatment of TNBC. Here, we performed an NMR spectroscopy–based metabolomics study to analyze the relationship between the patients’ metabolic phenotypes and chemotherapy sensitivity in the serum samples. Metabolic phenotypes from patients with pathological partial response, pathological complete response, and pathological stable disease (pPR, pCR, and pSD) could be distinguished. Furthermore, we conducted metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with three groups of TNBC patients. We evaluated the discriminative ability of metabolites related to significantly disturbed metabolic pathways by using the multi-receiver–operating characteristic (ROC) curve analysis. Three significantly disturbed metabolic pathways of glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, and alanine, aspartate, and glutamate metabolism could be used as potential predictive models to distinguish three types of TNBC patients. These results indicate that a metabolic phenotype could be used to predict whether a patient is suitable for NAC. Metabolomics research could provide data in support of metabolic phenotypes for personalized treatment of TNBC.
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Affiliation(s)
- Xiangming He
- The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU), Hangzhou, China.,Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Jinping Gu
- Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China
| | - Dehong Zou
- Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Hongjian Yang
- Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Yongfang Zhang
- Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Yuqing Ding
- Chinese Academy of Sciences, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Lisong Teng
- The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU), Hangzhou, China
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Nannini G, Meoni G, Tenori L, Ringressi MN, Taddei A, Niccolai E, Baldi S, Russo E, Luchinat C, Amedei A. Fecal metabolomic profiles: A comparative study of patients with colorectal cancer vs adenomatous polyps. World J Gastroenterol 2021; 27:6430-6441. [PMID: 34720532 PMCID: PMC8517777 DOI: 10.3748/wjg.v27.i38.6430] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/17/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC), the third most common cause of death in both males and females worldwide, shows a positive response to therapy and usually a better prognosis when detected at an early stage. However, the survival rate declines when the diagnosis is late and the tumor spreads to other organs. Currently, the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers, but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis. Due to its high sensitivity and precision, colonoscopy is currently the gold-standard screening technique for CRC, but it is a costly and invasive procedure. Therefore, the implementation of custom-made methodologies including those with minimal invasiveness, protection, and reproducibility is highly desirable. With regard to other screening methods, the screening of fecal samples has several benefits, and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences, genetic modifications, and environmental factors.
AIM To characterize the variation groups and potentially recognize some diagnostic markers, we compared with healthy controls (HCs) the fecal nuclear magnetic resonance (NMR) metabolomic profiles of patients with CRC or adenomatous polyposis (AP).
METHODS Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profiles of 32 CRC patients, 16 AP patients, and 38 HCs well matched in age, sex, and body mass index.
RESULTS NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients, AP patients, and HCs, and some discriminatory metabolites including acetate, butyrate, propionate, 3-hydroxyphenylacetic acid, valine, tyrosine and leucine were identified.
CONCLUSION In conclusion, we are confident that our data can be a forerunner for future studies on CRC management, especially the diagnosis and evaluation of the effectiveness of treatments.
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Affiliation(s)
- Giulia Nannini
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Gaia Meoni
- Department of Chemistry “Ugo Schiff”, University of Florence, Florence 50134, Italy
| | - Leonardo Tenori
- Department of Chemistry “Ugo Schiff”, University of Florence, Florence 50134, Italy
| | - Maria Novella Ringressi
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Antonio Taddei
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Elena Niccolai
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Simone Baldi
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Edda Russo
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Claudio Luchinat
- Department of Chemistry & Magnetic Resonance Center (CERM), University of Florence, Florence 50134, Italy
| | - Amedeo Amedei
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
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Yang Y, Gu X, Li Z, Zheng C, Wang Z, Zhou M, Chen Z, Li M, Li D, Xiang J. Whole-exome sequencing of rectal cancer identifies locally recurrent mutations in the Wnt pathway. Aging (Albany NY) 2021; 13:23262-23283. [PMID: 34642262 PMCID: PMC8544332 DOI: 10.18632/aging.203618] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 09/29/2021] [Indexed: 12/29/2022]
Abstract
Locally recurrent rectal cancer (LRRC) leads to a poor prognosis and appears as a clinically predominant pattern of failure. In this research, whole-exome sequencing (WES) was performed on 21 samples from 8 patients to search for the molecular mechanisms of LRRC. The data was analyzed by bioinformatics. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the candidate genes. Immunohistochemistry was used to detect the protein expression of LEF1 and CyclinD1 in LRRC, primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) specimens. The results showed that LRRC, PRC, and NRRC had 668, 794, and 190 specific genes, respectively. FGFR1 and MYC have copy number variants (CNVs) in PRC and LRRC, respectively. LRRC specific genes were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and ATP binding. The specific signaling pathways of LRRC were Wnt signaling pathway, gap junction, and glucagon signaling pathway, etc. The transcriptional and translational expression levels of genes including NFATC1, PRICKLE1, SOX17, and WNT6 related to Wnt signaling pathway were higher in rectal cancer (READ) tissues than normal rectal tissues. The PRICKLE1 mutation (c.C875T) and WNT6 mutation (c.G629A) were predicted as “D (deleterious)”. Expression levels of LEF1 and cytokinin D1 proteins: LRRC > PRC > NRRC > normal rectal tissue. Gene variants in the Wnt signaling pathway may be critical for the development of LRRC. The present study may provide a basis for the prediction of LRRC and the development of new therapeutic drugs.
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Affiliation(s)
- Yi Yang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Xiaodong Gu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Zhenyang Li
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Chuang Zheng
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Zihao Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Minwei Zhou
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Zongyou Chen
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Mengzhen Li
- MyGene Diagnostics Co., Ltd, Guangzhou 510000, China
| | - Dongbing Li
- MyGene Diagnostics Co., Ltd, Guangzhou 510000, China
| | - Jianbin Xiang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
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41
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Beklen H, Yildirim E, Kori M, Turanli B, Arga KY. Systems-level biomarkers identification and drug repositioning in colorectal cancer. World J Gastrointest Oncol 2021. [DOI: 10.4251/wjgo.v13.i7.463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Beklen H, Yildirim E, Kori M, Turanli B, Arga KY. Systems-level biomarkers identification and drug repositioning in colorectal cancer. World J Gastrointest Oncol 2021; 13:638-661. [PMID: 34322194 PMCID: PMC8299930 DOI: 10.4251/wjgo.v13.i7.638] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the most commonly diagnosed fatal cancer in both women and men worldwide. CRC ranked second in mortality and third in incidence in 2020. It is difficult to diagnose CRC at an early stage as there are no clinical symptoms. Despite advances in molecular biology, only a limited number of biomarkers have been translated into routine clinical practice to predict risk, prognosis and response to treatment. In the last decades, systems biology approaches at the omics level have gained importance. Over the years, several biomarkers for CRC have been discovered in terms of disease diagnosis and prognosis. On the other hand, a few drugs are being developed and used in clinics for the treatment of CRC. However, the development of new drugs is very costly and time-consuming as the research and development takes about 10 years and more than $1 billion. Therefore, drug repositioning (DR) could save time and money by establishing new indications for existing drugs. In this review, we aim to provide an overview of biomarkers for the diagnosis and prognosis of CRC from the systems biology perspective and insights into DR approaches for the prevention or treatment of CRC.
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Affiliation(s)
- Hande Beklen
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Esra Yildirim
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Medi Kori
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Beste Turanli
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
| | - Kazim Yalcin Arga
- Department of Bioengineering, Marmara University, Istanbul 34722, Turkey
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43
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Eskandrani AA. Effect of supplementing fava bean ( Vicia faba L.) on ulcerative colitis and colonic mucosal DNA content in rats fed a high-sucrose diet. Saudi J Biol Sci 2021; 28:3497-3504. [PMID: 34121890 PMCID: PMC8176050 DOI: 10.1016/j.sjbs.2021.03.017] [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: 11/14/2020] [Revised: 03/03/2021] [Accepted: 03/07/2021] [Indexed: 12/21/2022] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease with high morbidity. Acetic acid-induced damage of colonic mucosa in rats is a commonly used experimental animal model of UC. This research aimed to explore for the first time the ameliorative effect of dietary supplementation with fava bean on the incidence of UC in rats fed with sucrose containing diet. Rats were divided into five groups as follows: G1, control healthy rats; G2, colitic rats; G3, colitic rats fed diets containing 30% sucrose, G4, healthy rats fed diets containing 30% sucrose and G5, colitic rats fed diets containing 30% sucrose supplemented with dried ground fava bean. Colonic injury and inflammation were evaluated through a disturbance of oxidative biomarkers, a significant increase in inflammatory biomarkers and inflammatory cytokines, and histological abnormalities in colonic tissues accompanied by colonic mucosal DNA damage. Colitic rats fed on sucrose containing diet demonstrated additional histological, biochemical, and DNA alterations in colonic mucosa of rats. Dietary supplementation with dried ground fava bean significantly corrected the impaired oxidative and inflammatory biomarker levels and modulated histological features and DNA alterations. Finally, fava bean attenuated the oxidative damage and colonic injury induced by acetic acid, which confirmed its high anti-oxidant and anti-incendiary properties.
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Affiliation(s)
- Areej A Eskandrani
- Chemistry Department, College of Science, Taibah University, Medina 30002, Saudi Arabia
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Abstract
Nuclear magnetic resonance (NMR) spectroscopy offers reproducible quantitative analysis and structural identification of metabolites in various complex biological samples, such as biofluids (plasma, serum, and urine), cells, tissue extracts, and even intact organs. Therefore, NMR-based metabolomics, a mainstream metabolomic platform, has been extensively applied in many research fields, including pharmacology, toxicology, pathophysiology, nutritional intervention, disease diagnosis/prognosis, and microbiology. In particular, NMR-based metabolomics has been successfully used for cancer research to investigate cancer metabolism and identify biomarker and therapeutic targets. This chapter highlights the innovations and challenges of NMR-based metabolomics platform and its applications in cancer research.
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45
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Răchieriu C, Eniu DT, Moiş E, Graur F, Socaciu C, Socaciu MA, Hajjar NA. Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI +MS. Biomolecules 2021; 11:biom11030417. [PMID: 33799830 PMCID: PMC8035671 DOI: 10.3390/biom11030417] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/02/2021] [Accepted: 03/08/2021] [Indexed: 12/15/2022] Open
Abstract
Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI+ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the “lipogenic phenotype” specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.
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Affiliation(s)
- Claudiu Răchieriu
- Surgery Department, County Hospital Alba, 510118 Alba Iulia, Romania;
- Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400015 Cluj-Napoca, Romania; (E.M.); (F.G.); (N.A.H.)
| | - Dan Tudor Eniu
- Oncology Department, Iuliu Hațieganu University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;
| | - Emil Moiş
- Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400015 Cluj-Napoca, Romania; (E.M.); (F.G.); (N.A.H.)
| | - Florin Graur
- Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400015 Cluj-Napoca, Romania; (E.M.); (F.G.); (N.A.H.)
| | - Carmen Socaciu
- University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
- Research Center for Applied Biotechnology in Diagnosis and Molecular Therapy, 400478 Cluj-Napoca, Romania
- Correspondence: (C.S.); (M.A.S.)
| | - Mihai Adrian Socaciu
- Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400015 Cluj-Napoca, Romania; (E.M.); (F.G.); (N.A.H.)
- Correspondence: (C.S.); (M.A.S.)
| | - Nadim Al Hajjar
- Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400015 Cluj-Napoca, Romania; (E.M.); (F.G.); (N.A.H.)
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Gumpenberger T, Brezina S, Keski-Rahkonen P, Baierl A, Robinot N, Leeb G, Habermann N, Kok DEG, Scalbert A, Ueland PM, Ulrich CM, Gsur A. Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas. Metabolites 2021; 11:119. [PMID: 33669644 PMCID: PMC7922413 DOI: 10.3390/metabo11020119] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/09/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the "Metabolomic profiles throughout the continuum of colorectal cancer" (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the "Colorectal Cancer Study of Austria" (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.
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Affiliation(s)
- Tanja Gumpenberger
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria; (T.G.); (S.B.)
| | - Stefanie Brezina
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria; (T.G.); (S.B.)
| | - Pekka Keski-Rahkonen
- International Agency for Research on Cancer, 69372 Lyon, France; (P.K.-R.); (N.R.); (A.S.)
| | - Andreas Baierl
- Department of Statistics and Operations Research, University of Vienna, 1090 Vienna, Austria;
| | - Nivonirina Robinot
- International Agency for Research on Cancer, 69372 Lyon, France; (P.K.-R.); (N.R.); (A.S.)
| | - Gernot Leeb
- Department of Internal Medicine, Hospital Oberpullendorf, 7350 Oberpullendorf, Austria;
| | - Nina Habermann
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- Genome Biology, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany
| | - Dieuwertje E G Kok
- Division of Human Nutrition and Health, Wageningen University & Research, 6708 Wageningen, The Netherlands;
| | - Augustin Scalbert
- International Agency for Research on Cancer, 69372 Lyon, France; (P.K.-R.); (N.R.); (A.S.)
| | | | - Cornelia M Ulrich
- Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA;
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84108, USA
| | - Andrea Gsur
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria; (T.G.); (S.B.)
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Gallardo-Gómez M, De Chiara L, Álvarez-Chaver P, Cubiella J. Colorectal cancer screening and diagnosis: omics-based technologies for development of a non-invasive blood-based method. Expert Rev Anticancer Ther 2021; 21:723-738. [PMID: 33507120 DOI: 10.1080/14737140.2021.1882858] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Colorectal cancer (CRC) is one of the most important health problems in the Western world. In order to reduce the burden of the disease, two strategies are proposed: screening and prompt detection in symptomatic patients. Although diagnosis and prevention are mainly based on colonoscopy, fecal hemoglobin detection has been widely implemented as a noninvasive strategy. Various studies aiming to discover blood-based biomarkers have recently emerged.Areas covered: The burgeoning omics field provides diverse high-throughput approaches for CRC blood-based biomarker discovery. In this review, we appraise the most robust and commonly used technologies within the fields of genomics, transcriptomics, epigenomics, proteomics, and metabolomics, together with their targeted validation approaches. We summarize the transference process from the discovery phase until clinical translation. Finally, we review the best candidate biomarkers and their potential clinical applicability.Expert opinion: Some available biomarkers are promising, especially in the field of epigenomics: DNA methylation and microRNA. Transference requires the joint collaboration of basic researchers, intellectual property experts, technology transfer officers and clinicians. Blood-based biomarkers will be selected not only based on their diagnostic accuracy and cost but also on their reliability, applicability to clinical analysis laboratories and their acceptance by the population.
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Affiliation(s)
- María Gallardo-Gómez
- Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.,Biomedical Research Center (CINBIO), University of Vigo, Vigo, Spain
| | - Loretta De Chiara
- Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.,Biomedical Research Center (CINBIO), University of Vigo, Vigo, Spain
| | - Paula Álvarez-Chaver
- Proteomics Unit, Service of Structural Determination, Proteomics and Genomics, Center for Scientific and Technological Research Support (CACTI), University of Vigo, Vigo, Spain
| | - Joaquin Cubiella
- Department of Gastroenterology, Hospital Universitario De Ourense, Ourense, Spain.,Instituto De Investigación Sanitaria Galicia Sur, Ourense, Spain.,Centro De Investigación Biomédica En Red Enfermedades Hepáticas Y Digestivas, Ourense, Spain
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48
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Kumar P, Kumar V. Role of NMR Metabolomics and MR Imaging in Colon Cancer. COLON CANCER DIAGNOSIS AND THERAPY 2021:43-66. [DOI: 10.1007/978-3-030-63369-1_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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49
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Urinary charged metabolite profiling of colorectal cancer using capillary electrophoresis-mass spectrometry. Sci Rep 2020; 10:21057. [PMID: 33273632 PMCID: PMC7713069 DOI: 10.1038/s41598-020-78038-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 11/19/2020] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) has increasing global prevalence and poor prognostic outcomes, and the development of low- or less invasive screening tests is urgently required. Urine is an ideal biofluid that can be collected non-invasively and contains various metabolite biomarkers. To understand the metabolomic profiles of different stages of CRC, we conducted metabolomic profiling of urinary samples. Capillary electrophoresis-time-of-flight mass spectrometry was used to quantify hydrophilic metabolites in 247 subjects with stage 0 to IV CRC or polyps, and healthy controls. The 154 identified and quantified metabolites included metabolites of glycolysis, TCA cycle, amino acids, urea cycle, and polyamine pathways. The concentrations of these metabolites gradually increased with the stage, and samples of CRC stage IV especially showed a large difference compared to other stages. Polyps and CRC also showed different concentration patterns. We also assessed the differentiation ability of these metabolites. A multiple logistic regression model using three metabolites was developed with a randomly designated training dataset and validated using the remaining data to differentiate CRC and polys from healthy controls based on a panel of urinary metabolites. These data highlight the changes in metabolites from early to late stage of CRC and also the differences between CRC and polyps.
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50
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Dalal N, Jalandra R, Sharma M, Prakash H, Makharia GK, Solanki PR, Singh R, Kumar A. Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives. Biomed Pharmacother 2020; 131:110648. [PMID: 33152902 DOI: 10.1016/j.biopha.2020.110648] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/09/2020] [Accepted: 08/16/2020] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) ranks third among the most commonly occurring cancers worldwide, and it causes half a million deaths annually. Alongside mechanistic study for CRC detection and treatment by conventional techniques, new technologies have been developed to study CRC. These technologies include genomics, transcriptomics, proteomics, and metabolomics which elucidate DNA markers, RNA transcripts, protein and, metabolites produced inside the colon and rectum part of the gut. All these approaches form the omics arena, which presents a remarkable opportunity for the discovery of novel prognostic, diagnostic and therapeutic biomarkers and also delineate the underlying mechanism of CRC causation, which may further help in devising treatment strategies. This review also mentions the latest developments in metagenomics and culturomics as emerging evidence suggests that metagenomics of gut microbiota has profound implications in the causation, prognosis, and treatment of CRC. A majority of bacteria cannot be studied as they remain unculturable, so culturomics has also been strengthened to develop culture conditions suitable for the growth of unculturable bacteria and identify unknown bacteria. The overall purpose of this review is to succinctly evaluate the application of omics technologies in colorectal cancer research for improving the diagnosis and treatment strategies.
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Affiliation(s)
- Nishu Dalal
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India; Department of Environmental Science, Satyawati College, Delhi University, Delhi 110052, India
| | - Rekha Jalandra
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India; Department of Zoology, Maharshi Dayanand University, Rohtak 124001, India
| | - Minakshi Sharma
- Department of Zoology, Maharshi Dayanand University, Rohtak 124001, India
| | - Hridayesh Prakash
- Amity Institute of Virology and Immunology, Amity University, Sector 125, Noida 201313, Uttar Pradesh, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Pratima R Solanki
- Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi 110067, India
| | - Rajeev Singh
- Department of Environmental Science, Satyawati College, Delhi University, Delhi 110052, India.
| | - Anil Kumar
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India.
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