Tumor metabolism, a crucial component in cancer progression, represents a potential prognostic and diagnostic platform in cancer detection. Here, we show that patient-specific stromal mesenchymal cells exhibit distinct behaviors in promoting either tumor growth or dissemination. Tumor-associated fibroblasts (TAFs) isolated from non-metastasized colorectal adenocarcinomas predominantly supported cancer cell proliferation, whereas TAFs isolated from metastatic adenocarcinomas facilitated cancer cell migration. An in vitro analysis of stromal paracrine factors revealed that variations in mitochondrial activity and the secretion of specific metabolites were closely associated with distinct tumor-stroma interactions.
Among the oncometabolites identified, we validated amino acid expression in urine samples from 19 colon cancer patients to assess their potential as diagnostic biomarkers.
Our results showed patient-specific alterations in oncometabolite expression, which were significantly different from those of healthy control individuals. The specificity, sensitivity, and accuracy analysis indicated 93-100% specificity, 74-82% sensitivity, and 84-89% accuracy of single metabolites in distinguishing cancer patients from healthy controls. While no false negatives were observed, urine samples from nine patients with various inflammatory conditions (including diverticulitis, appendicitis, and chronic gastritis) yielded false positives. Sensitivity analysis and the t-Distributed Stochastic Neighbor Embedding (t-SNE) nonlinear dimensionality reduction technique revealed distinct metabolite profiles for healthy controls, colon cancer patients, and patients diagnosed with inflammation.
Overall, our findings suggest that the identified oncometabolites, when integrated into a biomarker panel, hold promise as a novel non-invasive tool for screening individuals at risk of cancer and inflammatory malignancies.
AbstractTumor metabolism, a crucial component in cancer progression, represents a potential prognostic and diagnostic platform in cancer detection. Here, we show that patient-specific stromal mesenchymal cells exhibit distinct behaviors in promoting either tumor growth or dissemination. Tumor-associated fibroblasts (TAFs) isolated from non-metastasized colorectal adenocarcinomas predominantly supported cancer cell proliferation, whereas TAFs isolated from metastatic adenocarcinomas facilitated cancer cell migration. An in vitro analysis of stromal paracrine factors revealed that variations in mitochondrial activity and the secretion of specific metabolites were closely associated with distinct tumor-stroma interactions. Among the oncometabolites identified, we validated amino acid expression in urine samples from 19 colon cancer patients to assess their potential as diagnostic biomarkers. Our results showed patient-specific alterations in oncometabolite expression, which were significantly different from those of healthy control individuals. The specificity, sensitivity, and accuracy analysis indicated 93–100% specificity, 74–82% sensitivity, and 84–89% accuracy of single metabolites in distinguishing cancer patients from healthy controls. While no false negatives were observed, urine samples from nine patients with various inflammatory conditions (including diverticulitis, appendicitis, and chronic gastritis) yielded false positives. Sensitivity analysis and the t-Distributed Stochastic Neighbor Embedding (t-SNE) nonlinear dimensionality reduction technique revealed distinct metabolite profiles for healthy controls, colon cancer patients, and patients diagnosed with inflammation. Overall, our findings suggest that the identified oncometabolites, when integrated into a biomarker panel, hold promise as a novel non-invasive tool for screening individuals at risk of cancer and inflammatory malignancies.
Similar content being viewed by others
Decoding cancer across scales with metabolomics
Article
20 February 2026
Targeting of TAMs: can we be more clever than cancer cells?
Article
Open access
08 November 2024
Signaling pathways in cancer metabolism: mechanisms and therapeutic targets
Article
Open access
10 May 2023
AcknowledgementsThe authors present their gratitude to health care personnel in the Clinica Mediterraneo, Naples, Italy for helping the collection of urine samples.FundingThe European Union and Campania Region POR CUP B63D18000210007, AIRC 23125, Sapienza University GA116154C8A94E3D, SM12117A75F3D1B2, and RG123188B0602C40.Author informationAuthors and AffiliationsDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyAlessia Parascandolo & Mikko O. LaukkanenDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, Laboratory affiliated to the Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, ItalyMaria C. Magnifico & Francesca CutruzzolàIstituto Varelli, Naples, ItalyEmanuele De Vita & Marco VarelliDepartment of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USAPeiman HemattiInstitute of Applied Sciences and Intelligent Systems (ISASI), National Research Council (CNR), Lecce, ItalyCosimo DistanteClinica Mediterranea, Naples, ItalyFrancesco CorcioneDepartment of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, Rome, ItalyAlberto MaconeAuthorsAlessia ParascandoloView author publicationsSearch author on:PubMed Google ScholarMaria C. MagnificoView author publicationsSearch author on:PubMed Google ScholarEmanuele De VitaView author publicationsSearch author on:PubMed Google ScholarPeiman HemattiView author publicationsSearch author on:PubMed Google ScholarCosimo DistanteView author publicationsSearch author on:PubMed Google ScholarFrancesco CorcioneView author publicationsSearch author on:PubMed Google ScholarMarco VarelliView author publicationsSearch author on:PubMed Google ScholarFrancesca CutruzzolàView author publicationsSearch author on:PubMed Google ScholarAlberto MaconeView author publicationsSearch author on:PubMed Google ScholarMikko O. LaukkanenView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to
Mikko O. Laukkanen.Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics
Ethical approvals for the isolation of the primary cells, tissues, and for the urine sample collection were obtained from the ethical committees of the Monaldi Hospital, Naples, Italy (Project 2013-01-02, deliberation number 1293), the University of Federico II of Naples, Naples, Italy (Protocol 394/19), and the Clinical Mediterranea hospital, Naples, Italy (Authorization released by Medical Director on 24.5.2023). Informed consent was obtained from all participating patients. The study was performed in accordance with the Declaration of Helsinki. The funders had no role in the study’s design, execution, data analysis, or interpretation of the results.
Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplemetary file texts (download DOCX )Supplementary files (download PDF )Materials and Methods (download DOCX )Original Western blots (download JPG )Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Reprints and permissionsAbout this articleCite this articleParascandolo, A., Magnifico, M.C., De Vita, E. et al. Oncometabolite signatures from tumor-stroma crosstalk as potential non-invasive biomarkers.
Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03172-1Download citationReceived: 18 August 2025Revised: 13 April 2026Accepted: 15 May 2026Published: 22 May 2026DOI: https://doi.org/10.1038/s41420-026-03172-1
¡Aún no hay comentarios. Sé el primero en comentar!