{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:32Z","timestamp":1783660412383,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Organ-preservation strategies in locally advanced rectal cancer (LARC) increasingly require accurate assessment of response to neoadjuvant therapy, yet magnetic resonance imaging poorly distinguishes complete from near-complete responses. We investigated plasma sphingolipid dynamics across multiple treatment timepoints as monitoring biomarkers for pathological response. Methods: This single-centre cohort study included 86 patients with histologically confirmed LARC; 58 received neoadjuvant treatment followed by surgical resection with an evaluable Mandard tumour regression grade (TRG) and formed the response-evaluable cohort (19 good responders [TRG 1\u20132], 39 poor [TRG 3\u20135]). Plasma sphingomyelin (SM), sphingosine-1-phosphate and glucosylceramide were quantified by UPLC\u2013MS\/MS at baseline (M0), post-chemoradiotherapy (M1) and post-surgery (M2). Discrimination was assessed by receiver operating characteristic analysis and odds ratios, longitudinal trajectories by a linear mixed-effects model, and SM was compared head-to-head with serum carcinoembryonic antigen (CEA). Results: SM did not discriminate response at baseline (M0 AUC = 0.53) but did after treatment (M1 AUC = 0.750, p = 0.024; M2 AUC = 0.786, p = 0.010; pooled AUC = 0.767; odds ratio 10.67 at a 164.0 mg\/L cutoff; negative predictive value 84%). SM correlated inversely with TRG grade (Spearman \u03c1 = \u22120.43, p = 0.016) and outperformed serum CEA (AUC 0.74 vs. 0.60). Trajectories diverged over time (mixed-model time \u00d7 group interaction p = 0.023) with no baseline difference (p = 0.96): good responders increased SM by +22.5% from M0 to M2, whereas poor responders declined by \u22128.4%. Conclusions: Plasma SM is not a pre-treatment predictor but emerges as a post-treatment monitoring biomarker for pathological response in LARC, supporting its integration into multimodal response assessment for organ-preservation decision-making. External validation in independent cohorts is warranted.<\/jats:p>","DOI":"10.3390\/cancers18132124","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:56:55Z","timestamp":1782838615000},"page":"2124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Sphingomyelin as a Post-Treatment Monitoring Biomarker for Pathological Response in Locally Advanced Rectal Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-7388","authenticated-orcid":false,"given":"Pedro","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"Colorectal Unit, Department of Surgery, Hospital de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio (ULSSA), Largo Professor Abel Salazar, 4099-001 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00facia","family":"Lacerda","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"},{"name":"Laborat\u00f3rio de Bioqu\u00edmica Gen\u00e9tica, Servi\u00e7o de Gen\u00e9tica Laboratorial, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es, Cl\u00ednica de Gen\u00e9tica e de Patologia, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio (ULSSA), 4099-001 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa D.","family":"Santos","sequence":"additional","affiliation":[{"name":"Colorectal Unit, Department of Surgery, Hospital de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio (ULSSA), Largo Professor Abel Salazar, 4099-001 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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