Changes In Serum CXCL13 Levels Are Associated With Outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment - 16/06/24

Doi : 10.1016/j.biopha.2024.116857

Sara Cabrero-de las Heras ^a,^b,^{^{1
Current address: IrsiCaixa AIDS Research Institute – Health Sciences Research Institute Germans Trias i Pujol (IGTP), Carretera de Canyet, s/n, 08916 Badalona, Spain.}}, Xavier Hernández-Yagüe ^c,^d, Andrea González ^e,^f, Ferran Losa ^g,^h, Gemma Soler ^h, Cristina Bugés ^e,^f, Iosune Baraibar ^i,^j, Anna Esteve ^e,^f,^k, Miguel Ángel Pardo-Cea ^l,^m, Anne Hansen Ree ^n,^o, Neus Martínez-Bosch ^p, Maria Nieva ^q, Eva Musulén ^r,^s, Sebastian Meltzer ⁿ, Tania Lobato ^e, Carla Vendrell-Ayats ^a,^b, Cristina Queralt ^a,^b, Pilar Navarro ^p,^t,^u, Clara Montagut ^q,^v, Ferran Grau-Leal ^a,^b, David Camacho ^w, Raquel Legido ^h, Núria Mulet-Margalef ^e,^f, Eva Martínez-Balibrea ^a,^b,^⁎
^a CARE program, Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, Carretera de Can Ruit, camí de les escoles s/n, Badalona 08916, Spain
^b ProCURE program, Catalan Institute of Oncology, Campus Can Ruti, Carretera de Can Ruit camí de les escoles s/n, Badalona 08916, Spain
^c Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Avinguda de França, s/n, Girona 17007, Spain
^d Precision Oncology Group (OncoGIR-Pro), Girona BiomedicaI Research Institute (IDIBGI-CERCA), Parc Hospitalari Martí i Julià, Carrer del Dr. Castany, s/n, Salt, Girona 17190, Spain
^e Medical Oncology Service, Catalan Institute of Oncology, Campus Can Ruti, Carretera de Can Ruti, camí de les escoles s/n, Badalona 08916, Spain
^f Badalona-Applied Research Group in Oncology (B-ARGO), Germans Trias I Pujol Research Institute (IGTP), Campus Can Ruti, Carretera de Can Ruit, camí de les escoles s/n, Badalona 08916, Spain
^g Medical Oncology Service, Hospital Sant Joan Despí – Moisès Broggi, C. d′Oriol Martorell, 12, Sant Joan Despí 08970, Spain
^h Medical Oncology Service, Catalan Institute of Oncology, Gran Vía de l′Hospitalet 199-203, L’Hospitalet de Llobregat 08908, Spain
ⁱ Vall d′Hebron Institute of Oncology (VHIO), Vall d′Hebron Barcelona Hospital Campus, Carrer de Natzaret, 115-117, Barcelona 08035, Spain
^j Medical Oncology Department, Vall d′Hebron University Hospital, Vall d′Hebron Barcelona Hospital Campus, Pg. de la Vall d′Hebron, 119, Barcelona 08035, Spain
^k Research Management Unit (UGR), Catalan Institute of Oncology, Gran Vía de l′Hospitalet 199-203, L’Hospitalet de Llobregat 08908, Spain
^l ProCURE Program, Catalan Institute of Oncology, Gran Vía de l′Hospitalet 199-203, L’Hospitalet de Llobregat 08908, Spain
^m Oncobell Program, Bellvitge Institute for Biomedical Research (IDIBELL), Gran Vía de l′Hospitalet 199-203, L’Hospitalet del Llobregat 08908, Spain
ⁿ Department of Oncology, Akershus University Hospital, P.O. Box 1000, Lørenskog 1478, Norway
^o University of Oslo, Problemveien 11, Oslo 0313, Norway
^p Cancer Research Program, Hospital del Mar Research Institute (IMIM), Unidad Asociada IIBB-CSIC, C/ del Dr. Aiguader, 88, Barcelona 08003, Spain
^q Medical Oncology Department, Hospital del Mar Research Institute, Pg. Marítim de la Barceloneta, 25, 29, Barcelona 08003, Spain
^r Hospital Universitari General de Catalunya-Grupo Quironsalud, Carrer de Pedro i Pons, 1, Sant Cugat del Vallès 08195, Spain
^s Institut de Recerca contra la Leucèmia Josep Carreras, Campus Can Ruti, Carretera de Can Ruti, camí de les escoles s/n, Badalona 08916, Spain
^t Instituto de Investigaciones Biomédicas de Barcelona –Centro Superior de Investigaciones Científicas (IIBB-CSIC), C/ del Rosselló, 161, Barcelona 08036, Spain
^u Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), C/ del Rosselló, 149, Barcelona 08036, Spain
^v CIBERONC, Universitat Pompeu Fabra, Passeig Maritim 25-29, Barcelona 08003, Spain
^w Unidad de Enfermería Clinica de Cirugia. Hospital Sant Joan Despí – Moisès Broggi, C. d′Oriol Martorell, 12, Sant Joan Despí 08970, Spain

^⁎Correspondence to: Dr Eva Martinez-Balibrea, ProCURE program, Catalan Institute of Oncology (ICO) and CARE program, Germans Trias i Pujol Research Institute (IGTP), Carretera de Can Ruti, camí de les escoles s/n, Badalona 08916, Spain.Dr Eva Martinez-Balibrea, ProCURE program, Catalan Institute of Oncology (ICO) and CARE program, Germans Trias i Pujol Research Institute (IGTP)Carretera de Can Ruti, camí de les escoles s/nBadalona08916Spain

Abstract

Metastatic colorectal cancer (mCRC) currently lacks reliable biomarkers for precision medicine, particularly for chemotherapy-based treatments. This study examines the behavior of 11 CXC chemokines in the blood of 104 mCRC patients undergoing first-line oxaliplatin-based treatment to pinpoint predictive and prognostic markers. Serum samples were collected before treatment, at response evaluation (EVAR), and at disease progression or last follow-up. Chemokines were assessed in all samples using a Luminex® custom panel. CXCL13 levels increased at EVAR in responders, while in non-responders it decreased. Increasing levels of CXCL13 at EVAR, independently correlated with improved progression-free survival (PFS) and overall survival (OS). Nanostring® analysis in primary tumor samples showed CXCL13 gene expression's positive correlation not only with gene profiles related to an immunogenic tumor microenvironment, increased B cells and T cells (mainly CD8+) but also with extended OS. In silico analysis using RNAseq data from liver metastases treated or not with neoadjuvant oxaliplatin-based combinations, and deconvolution analysis using the MCP-counter algorithm, confirmed CXCL13 gene expression's association with increased immune infiltration, improved OS, and Tertiary Lymphoid Structures (TLSs) gene signatures, especially in neoadjuvant-treated patients. CXCL13 analysis in serum from 36 oxaliplatin-treated patients from the METIMMOX study control arm, reported similar findings. In conclusion, the increase of CXCL13 levels in peripheral blood and its association with the formation of TLSs within the metastatic lesions, emerges as a potential biomarker indicative of the therapeutic efficacy in mCRC patients undergoing oxaliplatin-based treatment

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Highlights

•	In CRC, Oxalipatin-based combinations often fail due to resistance and/or toxicity.
•	Lack of biomarkers complicates treatment decision-making. .
•	We examined serum levels of 11 CXC chemokines in patients on oxaliplatin.
•	Increased CXCL13 levels correlate with response, prognosis, tumor immunity and TLSs.
•	CXCL13 may serve as a predictive and prognostic biomarker for treatment efficacy.

Le texte complet de cet article est disponible en PDF.

Abbreviations : ACTB, BRAF, CAPOX, CI, CRC, CT, DCs, DMMR -MSI-H, EGFR, ELR, FFPE, FLOX, FOLFOX, HER2, HPRT1, HR, ICD, IQR, IPW, KM, KRAS, MCRC, NF-kB, NKs, NRAS, NSCLC, OD, OS, PBMCs, PD-1, PFS, RMA, RNA, SsGSEA, TFH, TH1, TLS, TME, Tregs, TUB, VEGF

Keywords : Colorectal cancer, Oxaliplatin, predictive biomarkers, Luminex, CXCL13, Tertiary Lymphoid Structures (TLS)

Plan

Background

Patients and methods

Study design and patients

Sample collection, processing and storage

Luminex® analysis

CXCL13 in silico analysis

Nanostring experiments

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Declaration of Generative AI and AI-assisted technologies in the writing process

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Article 116857- juillet 2024 Retour au numéro

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Changes In Serum CXCL13 Levels Are Associated With Outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment - 16/06/24

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