{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:31:03Z","timestamp":1786336263287,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic lipid remodeling accompanies colorectal cancer (CRC), but whether circulating lipid alterations specifically distinguish metastatic from non-metastatic disease remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center prospective cross-sectional study enrolled newly diagnosed patients with non-metastatic CRC (nmCRC), metastatic CRC (mCRC), and healthy controls (HC) between September and December 2024. Two separate 1:1 nearest-neighbor propensity score matches used the same mCRC cohort as the anchor and histories of diabetes and hyperlipidemia as covariates. Matching was performed without replacement using a caliper of 0.2 on the raw propensity-score scale. Participant-level linkage generated 20 matched triplets. Fasting plasma samples underwent quantitative targeted lipidomic profiling. Primary lipid comparisons used matched-pair tests with comparison-specific Benjamini-Hochberg correction, and age- and sex-adjusted sensitivity analyses evaluated residual baseline imbalance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1,459 quantified lipids, 72 nominal differential lipids were identified in mCRC versus nmCRC, 186 in nmCRC versus HC, and 222 in mCRC versus HC using paired raw P&amp;lt;0.05. No lipid remained significant after false discovery rate correction in mCRC versus nmCRC, whereas 12 and 30 lipids remained significant in nmCRC versus HC and mCRC versus HC, respectively. After age and sex adjustment, the corresponding FDR-significant counts were 0, 10, and 9. Eight nominal candidates were shared across all three primary comparisons: BMP(14:0_20:0), BMP(14:0_20:1), Cer(d18:1\/26:1), PC(18:2_18:2), PC(18:3_20:1), PC(18:3_20:4), PC(20:0_22:5), and PI(20:0_20:4).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma lipidomic differences were most reproducible between patients with CRC and healthy controls, particularly between mCRC and HC. Lipid differences between mCRC and nmCRC remained exploratory and hypothesis-generating. These findings indicate systemic lipid remodeling in CRC but do not establish metastasis-specific plasma biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1917544","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:22:55Z","timestamp":1786335775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted plasma lipidomics in non-metastatic colorectal cancer, metastatic colorectal cancer, and healthy controls: an exploratory matched-triplet study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaodong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yin","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Radiology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanyi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Precision Medicine for Digestive System Tumors, Bishan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70067","article-title":"Colorectal cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0029","article-title":"Colon cancer, version 3.2024, NCCN Clinical Practice Guidelines in Oncology","volume":"22","author":"Benson","year":"2024","journal-title":"J Natl Compr Canc Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.03.005","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"37","author":"Cremolini","year":"2026","journal-title":"Ann Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.32604\/or.2022.027900","article-title":"The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment","volume":"30","author":"Zhong","year":"2022","journal-title":"Oncol Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1343061","article-title":"Altered lipid metabolism in APC-driven colorectal cancer: the potential for therapeutic intervention","volume":"14","author":"Kelson","year":"2024","journal-title":"Front Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.934145","article-title":"UHPLC-HRMS-based serum lipisdomics reveals novel biomarkers to assist in the discrimination between colorectal adenoma and cancer","volume":"12","author":"Chen","year":"2022","journal-title":"Front Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10060262","article-title":"Plasma lipid profile reveals plasmalogens as potential biomarkers for colon cancer screening","volume":"10","author":"Fernandes","year":"2020","journal-title":"Metabolites"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13223","article-title":"Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers","volume":"16","author":"Elmallah","year":"2022","journal-title":"Mol Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-021-03450-0","article-title":"From bedside to bench-practical considerations to avoid pre-analytical pitfalls and assess sample quality for high-resolution metabolomics and lipidomics analyses of body fluids","volume":"413","author":"Lehmann","year":"2021","journal-title":"Anal Bioanal Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100138","article-title":"Recommendations for good practice in MS-based lipidomics","volume":"62","author":"K\u00f6feler","year":"2021","journal-title":"J Lipid Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00628-3","article-title":"Introducing the lipidomics minimal reporting checklist","volume":"4","author":"McDonald","year":"2022","journal-title":"Nat Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100621","article-title":"The lipidomics reporting checklist: a framework for transparency of lipidomic experiments and repurposing resource data","volume":"65","author":"Kopczynski","year":"2024","journal-title":"J Lipid Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.S120001025","article-title":"Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures","volume":"61","author":"Liebisch","year":"2020","journal-title":"J Lipid Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"61","author":"von Elm","year":"2008","journal-title":"J Clin Epidemiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.941643","article-title":"The key role of sphingolipid metabolism in cancer: new therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance","volume":"12","author":"Li","year":"2022","journal-title":"Front Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-024-02960-x","article-title":"How ceramides affect the development of colon cancer: from normal colon to carcinoma","volume":"476","author":"Merz","year":"2024","journal-title":"Pflugers Arch"},{"key":"B18","doi-asserted-by":"publisher","first-page":"16249","DOI":"10.1038\/s41598-023-43557-1","article-title":"Ceramide synthase CERS4 gene downregulation is associated with KRAS mutation in colorectal cancer","volume":"13","author":"Hayama","year":"2023","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00109-008-0409-0","article-title":"Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer","volume":"87","author":"Mansilla","year":"2009","journal-title":"J Mol Med (Berl)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1039\/D5MO00045A","article-title":"Advancing colorectal cancer research through lipidomics","volume":"21","author":"Santiago","year":"2025","journal-title":"Mol Omics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118095","article-title":"Lipid metabolism in cancer: exploring phospholipids as potential biomarkers","volume":"187","author":"Delmas","year":"2025","journal-title":"BioMed Pharmacother"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.cell.2024.01.030","article-title":"Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis","volume":"187","author":"Qiu","year":"2024","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjac.2023.100270","article-title":"Global serum metabolomic and lipidomic analyses reveal lipid perturbations and potential biomarkers of the colorectal cancer by adenoma-carcinoma sequence","volume":"51","author":"Zhu","year":"2023","journal-title":"Chin J Anal Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2024.115978","article-title":"Distinct plasma molecular profiles between early-onset and late-onset colorectal cancer patients revealed by metabolic and lipidomic analyses","volume":"241","author":"Zhang","year":"2024","journal-title":"J Pharm BioMed Anal"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.35449","article-title":"Targeted plasma lipidomic profiles associated with colorectal cancer risk and effect modifications by common risk factors and particulate matter exposure","volume":"157","author":"Zhou","year":"2025","journal-title":"Int J Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1136\/gutjnl-2024-332535","article-title":"Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer","volume":"74","author":"Soundararajan","year":"2025","journal-title":"Gut"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.114150","article-title":"Regulatory role of phosphatidylcholine metabolic reprogramming in colorectal cancer progression and neutrophil interactions","volume":"28","author":"Cheng","year":"2025","journal-title":"iScience"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1917544\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:22:56Z","timestamp":1786335776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1917544\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":28,"alternative-id":["10.3389\/fonc.2026.1917544"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1917544","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1917544"}}