CD44v6 is associated with tumor aggressiveness and chemoresistance in bladder cancer

Sep 22, 2026

Bladder cancer is a fast-moving, recurrent malignancy in which survival depends on early detection and accurate risk stratification, driving urgent biomarker discovery. This study investigates how CD44v6 expression relates to clinical features and functional behaviors in bladder cancer. Integrated analyses of patient samples and cell lines show that high CD44v6 expression predicts worse outcomes, promotes migratory and invasive activity, and increases resistance to cisplatin. CD44v6 is proposed as a prognostic biomarker and potential therapeutic target, supporting translational research into its mechanistic role in aggressiveness and chemoresistance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN CD44v6 is associated with tumor aggressiveness and chemoresistance in bladder cancer Iris Lodewijk1,2,3, Carolina Rubio1,2,11􀀍, Pontus Eriksson4, Ignacio A. Reina1,2,3, Esther Montesinos1,2, Miguel Alonso-Sánchez1,2, Laura García-Gómez1,2,Álvaro Martín de Bernardo1,2, Lucía Morales1,2,3, Cristian Suárez-Cabrera1,2,3, Mercedes Pérez-Escavy1,2,3, OmairaAlberquilla5,6, Rebeca Sánchez-Domínguez5, Félix Guerrero-Ramos7, Rosa García-Martin8, Lucía Parrilla8, José L. Rodríguez-Peralto3,8, Daniel Castellano7, Jesús M. Paramio1,2,3, Gottfrid Sjödahl9,10 & Marta Dueñas1,2,3,11􀀍 Bladder cancer is a fast-moving and recurrent malignancy where survival hinges on early detection and precise risk stratification. The search for robust biomarkers is urgent, and CD44v6 has emerged as a compelling candidate. In this study, we explored the clinical and functional associations of CD44v6 expression in bladder cancer. Integrated analyses of patient samples and cell lines showed that high CD44v6 expression is strongly associated with poor patient outcomes, enhanced migratory and invasive behavior, and increased resistance to cisplatin. These results suggest that CD44v6 may serve as a prognostic biomarker and a potential therapeutic target in bladder cancer. Overall, our findings highlight the translational relevance of CD44v6 and provide a foundation for future studies aimed at elucidating the mechanistic pathways underlying its role in tumor aggressiveness and chemoresistance. Keywords Urothelial Cancer, Prognosis, TAA, CD44v6, Targeted therapy Abbreviations BC Bladder cancer NMIBC non-muscle-invasive BC MIBC muscle-invasive BC mBC metastatic stage ADCs antibody-drug conjugates EV enfortumab vedotin SG sacituzumab govitecan OS overall survival ORR objective response rate TAAs tumor-associated antigens CD44s CD44 standard CSCs cancer stem cells HNSCC head and neck squamous cell carcinoma CAR chimeric antigen receptor 1Cellular and Molecular Oncology and Genitourinary Tumor Group, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Av. Complutense 40, 28040 Madrid, Spain. 2Molecular and Translational Oncology Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain. 3Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. 4Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden. 5Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédicaen Red de Enfermedades Raras (CIBER-ER), Madrid, Spain. 6Advanced Therapy Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD/UAM), Madrid, Spain. 7Uro-Oncology Unit, Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain. 8Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 9Department of Translational Medicine, Lund University, Malmö, Sweden. 10Department of Urology, Skåne University Hospital, Malmö, Sweden. 11Molecular Oncology Unit, Biomedical Innovation Department, CIEMAT, Av. Complutense 40, Madrid 28040, Spain. 􀀍 email: [carolina.rubio@ciemat.es](carolina.rubio@ciemat.es); [marta.duenas@ciemat.es](marta.duenas@ciemat.es) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) TCGA The Cancer Genome Atlas RNAseq Ribonucleic Acid sequencing BLCA Bladder Urothelial Carcinoma RSEM RNA-Seq by Expectation-Maximization RetBioH Spanish Hospital Biobanks Network TAM tissue microarray FFPE formalin-fixed paraffin-embedded HS horse serum FBS fetal bovine serum MFI Median Fluorescence Intensity FMO Fluorescence Minus One PCA Principal component analysis GSVA Gene set variation analysis EMT epithelial-mesenchymal transition ECM Extracellular matrix CD44v CD44 variants HGF hepatocyte grow

FAQs

What clinical and functional associations were found for CD44v6 in bladder cancer?

Higher CD44v6 expression is strongly associated with poor patient outcomes, increased migratory and invasive behavior, and greater resistance to cisplatin.

How does the study support CD44v6 as a biomarker or treatment target?

The findings suggest CD44v6 can function as a prognostic biomarker and a potential therapeutic target, based on links between expression levels and aggressive/therapy-resistant phenotypes.

Why is early detection and risk stratification important in bladder cancer according to the document?

Survival depends on early detection and precise risk stratification, and the document emphasizes the need for robust biomarkers to guide this process.

Sep 22, 2026

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