{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:51:47Z","timestamp":1788954707468,"version":"build-2803163510"},"reference-count":20,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Fundamental Research Grant Scheme","award":["FRGS\/1\/2021\/SKK05\/UKM\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2021\/SKK05\/UKM\/02\/1"]}]},{"name":"The Ministry of Higher Education (MOHE), Malaysia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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&lt;AUC&lt;1. Benzoic acid, acetate, and lactate significantly differentiate CRA <jats:italic>vs.<\/jats:italic> normal, while adenosine, pentothenate, and linoleic acid are highly remarkable for CRA <jats:italic>vs.<\/jats:italic> CRC. The five most affected pathways for CRA <jats:italic>vs.<\/jats:italic> normal are glycoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis; D-glutamine and D-glutamate metabolism; and nitrogen metabolism. Meanwhile, pyruvate metabolism, glycolysis\/gluconeogenesis, glycerolipid metabolism, citrate\/TCA cycle, and alanine, aspartate, and glutamate metabolism were found to be altered in CRA <jats:italic>vs.<\/jats:italic> CRC. However, the association of suggested serum metabolites and altered pathways is still unknown. Despite promising emerging evidence, further validation studies in a diverse population with standardized methodology are needed to validate the findings.<\/jats:p>","DOI":"10.7717\/peerj.18043","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T08:57:47Z","timestamp":1726822667000},"page":"e18043","source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic performance of serum metabolites biomarker associated with colorectal adenoma: a systematic review"],"prefix":"10.7717","volume":"12","author":[{"given":"Maryam Fatimah","family":"Abu Bakar","sequence":"first","affiliation":[{"name":"Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia,  Cheras, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siok Fong","family":"Chin","sequence":"additional","affiliation":[{"name":"UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Cheras, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Makpol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia,  Cheras, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen Kit","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia,  Cheras, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azmawati","family":"Mohammed Nawi","sequence":"additional","affiliation":[{"name":"Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia,  Cheras, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"issue":"11","key":"10.7717\/peerj.18043\/ref-1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s11306-017-1265-0","article-title":"Altered metabolite levels and correlations in patients with colorectal cancer and polyps detected using seemingly unrelated regression analysis","volume":"13","author":"Chen","year":"2017","journal-title":"Metabolomics"},{"issue":"1","key":"10.7717\/peerj.18043\/ref-2","doi-asserted-by":"publisher","first-page":"100873","DOI":"10.1016\/j.aohep.2022.100873","article-title":"Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: systematic review and meta-analysis","volume":"28","author":"Contreras","year":"2023","journal-title":"Annals of Hepatology"},{"issue":"7","key":"10.7717\/peerj.18043\/ref-3","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/bjc.2016.243","article-title":"A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics","volume":"115","author":"Farshidfar","year":"2016","journal-title":"British Journal of Cancer"},{"key":"10.7717\/peerj.18043\/ref-4","doi-asserted-by":"publisher","first-page":"3491852","DOI":"10.1155\/2019\/3491852","article-title":"Metabolomics analysis in serum from patients with colorectal polyp and colorectal cancer by 1H-NMR spectrometry","volume":"2019","author":"Gu","year":"2019","journal-title":"Disease Markers"},{"key":"10.7717\/peerj.18043\/ref-5","doi-asserted-by":"publisher","first-page":"104741","DOI":"10.1016\/j.jprot.2022.104741","article-title":"Serum metabolite signatures in normal individuals and patients with colorectal adenoma or colorectal cancer using UPLC-MS\/MS method","volume":"270","author":"Guo","year":"2023","journal-title":"Journal of Proteomics"},{"issue":"17","key":"10.7717\/peerj.18043\/ref-6","doi-asserted-by":"publisher","first-page":"8471","DOI":"10.1073\/pnas.1813212116","article-title":"Conserved serum protein biomarkers associated with growing early colorectal adenomas","volume":"116","author":"Ivancic","year":"2019","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"R1","key":"10.7717\/peerj.18043\/ref-7","doi-asserted-by":"publisher","first-page":"R93","DOI":"10.1093\/hmg\/ddv263","article-title":"Genetics of human metabolism: an update","volume":"24","author":"Kastenm\u00fcller","year":"2015","journal-title":"Human Molecular Genetics"},{"issue":"2","key":"10.7717\/peerj.18043\/ref-8","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1053\/j.gastro.2020.04.004","article-title":"Increased risk of colorectal cancer in individuals with a history of serrated CRA","volume":"159","author":"Li","year":"2020","journal-title":"Gastroenterology"},{"issue":"5","key":"10.7717\/peerj.18043\/ref-9","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1021\/acs.jproteome.3c00006","article-title":"Quantification of serum metabolites in early colorectal adenomas using isobaric labeling mass spectrometry","volume":"22","author":"Liu","year":"2023","journal-title":"Journal of Proteome Research"},{"issue":"8","key":"10.7717\/peerj.18043\/ref-10","doi-asserted-by":"publisher","first-page":"e103910","DOI":"10.1371\/journal.pone.0103910","article-title":"A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer","volume":"9","author":"Liu","year":"2014","journal-title":"PLOS ONE"},{"issue":"20","key":"10.7717\/peerj.18043\/ref-11","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1002\/cncr.30829","article-title":"Global and targeted serum metabolic profiling of colorectal cancer progression","volume":"123","author":"Long","year":"2017","journal-title":"Cancer"},{"issue":"1","key":"10.7717\/peerj.18043\/ref-12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1515\/ijb-2020-0091","article-title":"The area under the generalized receiver-operating characteristic curve","volume":"18","author":"Mart\u00ednez-Camblor","year":"2022","journal-title":"The International Journal of Biostatistics"},{"key":"10.7717\/peerj.18043\/ref-13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.jclinepi.2021.02.003","article-title":"Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement","volume":"134","author":"Page","year":"2021","journal-title":"Journal of Clinical Epidemiology"},{"issue":"3","key":"10.7717\/peerj.18043\/ref-14","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.gtc.2018.04.004","article-title":"The natural history of colorectal polyp: overview of predictive static and dynamic features","volume":"47","author":"Pickhardt","year":"2018","journal-title":"Gastroenterology Clinics"},{"issue":"11","key":"10.7717\/peerj.18043\/ref-15","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1056\/NEJMra1513581","article-title":"Colorectal adenomas","volume":"374","author":"Strum","year":"2016","journal-title":"New England Journal of Medicine"},{"issue":"3","key":"10.7717\/peerj.18043\/ref-16","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2020","journal-title":"CA: a Cancer Journal for Clinicians"},{"issue":"3","key":"10.7717\/peerj.18043\/ref-17","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3390\/jcm11030721","article-title":"Changing metabolic patterns along the colorectal adenoma-carcinoma sequence","volume":"11","author":"Tevini","year":"2022","journal-title":"Journal of Clinical Medicine"},{"issue":"6","key":"10.7717\/peerj.18043\/ref-18","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s00535-016-1261-6","article-title":"Serum metabolomics analysis for early detection of colorectal cancer","volume":"52","author":"Uchiyama","year":"2017","journal-title":"Journal of Gastroenterology"},{"issue":"2","key":"10.7717\/peerj.18043\/ref-19","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/hir.12176","article-title":"Database selection in systematic reviews: an insight through clinical neurology","volume":"34","author":"Vassar","year":"2017","journal-title":"Health Information & Libraries Journal"},{"issue":"9","key":"10.7717\/peerj.18043\/ref-20","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1021\/pr500494u","article-title":"Colorectal cancer detection using targeted serum metabolic profiling","volume":"13","author":"Zhu","year":"2014","journal-title":"Journal of Proteome Research"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/18043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18043.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18043.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T08:57:59Z","timestamp":1726822679000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/18043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":20,"alternative-id":["10.7717\/peerj.18043"],"URL":"https:\/\/doi.org\/10.7717\/peerj.18043","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,20]]},"article-number":"e18043"}}