{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:10:02Z","timestamp":1788869402147,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bialystok","award":["B.SUB.25.501"],"award-info":[{"award-number":["B.SUB.25.501"]}]},{"award":["B.SUB.25.501"],"award-info":[{"award-number":["B.SUB.25.501"]}],"id":[{"id":"https:\/\/ror.org\/01qaqcf60","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Colorectal cancer (CRC) exhibits substantial metabolic heterogeneity, but the organization of sphingolipid remodeling remains incompletely understood. In this exploratory single-center study, we integrated patient-matched tissue lipidomics, systemic oxidative stress profiling, and independent transcriptomic analyses. Tumor tissue, adjacent non-neoplastic mucosa, and preoperative serum were collected from 40 patients with CRC, with serum obtained from 23 hospitalized non-cancer controls. Sphingolipids were quantified by UHPLC\u2013MS\/MS, while total antioxidant capacity, total oxidant status, and oxidative stress index characterized systemic redox status. Paired lipidomics revealed coordinated remodeling with increased S1P-associated measures, selective ceramide depletion, and elevated S1P-to-ceramide ratios. Multivariate analyses did not identify stable discrete lipidomic subgroups and revealed variation consistent with a continuum-like organization within the measured sphingolipid feature space. In separate principal component analyses, ratio-derived variables showed a more concentrated low-dimensional covariance structure than absolute lipid concentrations. Circulating sphingolipids showed limited correspondence with tumor-local remodeling, whereas oxidative stress markers showed strong apparent discrimination between CRC and hospitalized non-cancer controls, although this finding may be affected by residual confounding. TCGA\u2013GTEx analyses provided complementary pathway-level transcriptomic context, while anatomically resolved analysis of 374 TCGA tumors identified 3376 genes significantly associated with colorectal anatomical position, including six sphingolipid-related genes. Overall, these exploratory findings support a conceptual CRC Metabolic Continuum while requiring validation in larger, independent cohorts.<\/jats:p>","DOI":"10.3390\/antiox15091136","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:23:51Z","timestamp":1788866631000},"page":"1136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sphingolipid Remodeling in Colorectal Cancer Reveals a Continuum-like Metabolic Organization"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-5549","authenticated-orcid":false,"given":"Adam R.","family":"Markowski","sequence":"first","affiliation":[{"name":"Department of Hypertensiology, Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-540 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Karolina","family":"St\u0119pniak","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5217","authenticated-orcid":false,"given":"Piotr","family":"Zabielski","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Hady Razak","family":"Hady","sequence":"additional","affiliation":[{"name":"2nd Clinical Department of General, Gastroenterological, and Oncological Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5265-6245","authenticated-orcid":false,"given":"Aleksander","family":"\u0141ukaszewicz","sequence":"additional","affiliation":[{"name":"2nd Clinical Department of General, Gastroenterological, and Oncological Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Paulina","family":"G\u0142uszy\u0144ska","sequence":"additional","affiliation":[{"name":"2nd Clinical Department of General, Gastroenterological, and Oncological Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Patrycja","family":"Sadowska","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Urszula","family":"Chlabicz","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Agnieszka","family":"B\u0142achnio-Zabielska","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sies, H. 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