Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficac...

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Main Authors: Anna Wojakowska, Lukasz Marczak, Marcin Zeman, Mykola Chekan, Ewa Zembala-Nożyńska, Krzysztof Polanski, Aleksander Strugała, Piotr Widlak, Monika Pietrowska
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1323961/full
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author Anna Wojakowska
Lukasz Marczak
Marcin Zeman
Mykola Chekan
Ewa Zembala-Nożyńska
Krzysztof Polanski
Aleksander Strugała
Piotr Widlak
Monika Pietrowska
author_facet Anna Wojakowska
Lukasz Marczak
Marcin Zeman
Mykola Chekan
Ewa Zembala-Nożyńska
Krzysztof Polanski
Aleksander Strugała
Piotr Widlak
Monika Pietrowska
author_sort Anna Wojakowska
collection DOAJ
description BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
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spelling doaj.art-3f43c2ebf3f94730a7c3c985ab1dcc452024-02-12T20:25:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.13239611323961Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapyAnna Wojakowska0Lukasz Marczak1Marcin Zeman2Mykola Chekan3Ewa Zembala-Nożyńska4Krzysztof Polanski5Aleksander Strugała6Piotr Widlak7Monika Pietrowska8Laboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, PolandLaboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, PolandThe Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, PolandDepartment of Pathomorphology, University of Technology, Katowice, PolandTumor Pathology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, PolandWellcome Sanger Institute, Hinxton, Cambridge, United KingdomLaboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland2nd Department of Radiology, Medical University of Gdańsk, Gdańsk, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, PolandBackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.https://www.frontiersin.org/articles/10.3389/fonc.2024.1323961/fullrectal cancerradiotherapytissuemetabolomicsproteomics
spellingShingle Anna Wojakowska
Lukasz Marczak
Marcin Zeman
Mykola Chekan
Ewa Zembala-Nożyńska
Krzysztof Polanski
Aleksander Strugała
Piotr Widlak
Monika Pietrowska
Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
Frontiers in Oncology
rectal cancer
radiotherapy
tissue
metabolomics
proteomics
title Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
title_full Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
title_fullStr Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
title_full_unstemmed Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
title_short Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
title_sort proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
topic rectal cancer
radiotherapy
tissue
metabolomics
proteomics
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1323961/full
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