Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy

Sep 24, 2026

Rectal cancer has a poor prognosis, and understanding how tumors respond to treatment remains challenging. This study compared relative lipid abundance in rectal tumor tissue linked to neoadjuvant chemoradiotherapy response using untargeted liquid chromatography–mass spectrometry lipidomics. Locally advanced patients provided biopsies before and after nCRT, then samples were contrasted between responders and non-responders. Non-responders showed higher simple glycosphingolipids and altered glycerophospholipid residues, with oxidized glycerophospholipids particularly elevated after nCRT, identifying candidate lipids associated with nCRT failure.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Rectal cancer background and clinical burden

Need for biomolecules and personalized therapeutic strategies

Role of lipidomics and mass spectrometry in oncology

Article Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy Salvador S¡nchez-Vinces 1, Gustavo Henrique Bueno Duarte 1, Marcia Cristina Fernandes Messias 1, Caroline Fernanda Alves Gatinoni 1, Alex Ap. Rosini Silva 2, Pedro Henrique Godoy Sanches 2, Carlos Augusto Real Martinez 3, Andreia M. Porcari 2 and Patricia de Oliveira Carvalho 1, * Citation: Sánchez-Vinces, S.; Duarte, G.H.B.; Messias, M.C.F.; Gatinoni, C.F.A.; Silva, A.A.R.; Sanches, P.H.G.; Martinez, C.A.R.; Porcari, A.M.; Carvalho, P.d.O. Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy. Int. J. Mol. Sci. 2023, 24, 11479 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241411479 Academic Editors: Tiago Rodrigues and Roger Chammas Received: 28 May 2023 Revised: 30 June 2023 Accepted: 5 July 2023 Published: 14 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Health Sciences Postgraduate Program, S¢o Francisco University—USF, Bragança Paulista, S¢o Paulo 12916-900, Brazil; [salvador.vinces@mail.usf.edu.br](salvador.vinces@mail.usf.edu.br) (S.S.-V.); [gustavo_duarte95@hotmail.com](gustavo_duarte95@hotmail.com) (G.H.B.D.); [marcia.cfmessias@gmail.com](marcia.cfmessias@gmail.com) (M.C.F.M.); [carolgatinoni@gmail.com](carolgatinoni@gmail.com) (C.F.A.G.) 2 MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, S¢o Francisco University—USF, Bragança Paulista, S¢o Paulo 12916-900, Brazil; [alex.rosini@mail.usf.edu.br](alex.rosini@mail.usf.edu.br) (A.A.R.S.); [pedrohgodoys@gmail.com](pedrohgodoys@gmail.com) (P.H.G.S.); [andreia.porcari@usf.edu.br](andreia.porcari@usf.edu.br) (A.M.P.) 3 Department of Colorectal Surgery, S¢o Francisco University—USF, Bragança Paulista, S¢o Paulo 12916-900, Brazil; [carlos.martinez@usf.edu.br](carlos.martinez@usf.edu.br) * [Correspondence: patricia.carvalho@usf.edu.br](Correspondence: patricia.carvalho@usf.edu.br) Abstract: Rectal cancer (RC) is a gastrointestinal cancer with a poor prognosis. While some studies have shown metabolic reprogramming to be linked to RC development, it is difﬁcult to deﬁne biomolecules, like lipids, that help to understand cancer progression and response to therapy. The present study investigated the relative lipid abundance in tumoral tissue associated with neoadjuvant therapy response using untargeted liquid chromatography–mass spectrometry lipidomics. Locally advanced rectal cancer (LARC) patients (n = 13), clinically staged as T3–4 were biopsied before neoadjuvant chemoradiotherapy (nCRT) . Tissue samples collected before nCRT (staging) and afterwards (restaging) were analyzed to discover lipidomic differences in RC cancerous tissue from Responders (n = 7) and Non-responders (n = 6) to nCRT. The limma method was used to test differences between groups and to select relevant feature lipids from tissue samples. Simple glycosphingolipids and differences in some residues of glycerophospholipids were more abundant in the Non-responder group before and after nCRT. Oxidized glycerophospholipids were more abundant in samples of Non-responders, especially those collected after nCRT. This work identiﬁed potential lipids in tissue samples that take part in, or may explain, nCRT failure. These results could potentially provide a lipid-based explanation for nCRT response and also help in understanding the molecular basis of RC and nCRT effects on the tissue matrix. Keywords: rectal cancer; lipidomics; response to neoadjuvant therapy 1. Introduction Rectal cancer (RC) is one of the top four most deadly cancers worldwide [1] . In the last three decades, th

FAQs

What question does the study address?

How rectal cancer tissue lipidomes differ according to response to neoadjuvant chemoradiotherapy, and which lipids may relate to treatment failure.

How were patient samples collected and analyzed?

Locally advanced rectal cancer patients were biopsied before (staging) and after neoadjuvant chemoradiotherapy (restaging), and tissue lipids were profiled using untargeted LC–MS lipidomics.

What lipid differences were observed between responders and non-responders?

Non-responders had more simple glycosphingolipids and differences in glycerophospholipid residues both before and after nCRT, and oxidized glycerophospholipids were especially higher in non-responders after nCRT.

Sep 24, 2026

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