Luís Lima1, Manuel Neves2, Marta I Oliveira3, Lorena Dieguez3, Rui Freitas4, Rita Azevedo2, Cristiana Gaiteiro2, Janine Soares5, Dylan Ferreira5, Andreia Peixoto6, Elisabete Fernandes7, Diana Montezuma8, Ana Tavares9, Ricardo Ribeiro10, Ana Castro11, Manuel Oliveira12, Avelino Fraga12, Celso A Reis13, Lúcio Lara Santos14, José Alexandre Ferreira15. 1. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Porto Comprehensive Cancer Center (P.ccc), Porto, Portugal. Electronic address: luis14lima@gmail.com. 2. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal. 3. International Iberian Nanotechnology Laboratory, Braga, Portugal. 4. Department of Urology, Portuguese Institute of Oncology, Porto, Portugal. 5. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal. 6. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal; New Therapies Group, INEB-Institute for Biomedical Engineering, Porto, Portugal; Institute for Research and Innovation in Health, University of Porto, Porto, Portugal. 7. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Biomaterials for Multistage Drug and Cell Delivery, INEB-Institute for Biomedical Engineering, Porto, Portugal. 8. Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal. 9. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal. 10. Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Tumour and Microenvironment Interactions, INEB-Institute for Biomedical Engineering, Porto, Portugal; Laboratory of Genetics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Molecular Oncology Group, Portuguese Institute of Oncology, Porto, Portugal. 11. Department of Medical Oncology, Porto Hospital Centre, Hospital of Santo António, Porto, Portugal. 12. Department of Urology, Porto Hospital Centre, Hospital of Santo António, Porto, Portugal. 13. Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Department of Pathology and Oncology, Faculty of Medicine, Porto University, Porto, Portugal. 14. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Health School of University Fernando Pessoa, Porto, Portugal; Department of Surgical Oncology, Portuguese Institute of Oncology, Porto, Portugal. 15. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Institute of Oncology, Porto, Portugal; Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal; International Iberian Nanotechnology Laboratory, Braga, Portugal; Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Glycobiology in Cancer, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Porto Comprehensive Cancer Center (P.ccc), Porto, Portugal. Electronic address: jose.a.ferreira@ipoporto.min-saude.pt.
Abstract
OBJECTIVES: To evaluate the potential of sialyl-Tn (STn), a cancer-associated glycan antigen present in membrane glycoproteins, to improve a recent molecular model for stratification and prognostication of advanced stage bladder tumors based on keratins (KRT14, 5, and 20) expression. In addition, determine the association between STn and disease dissemination based on the evaluation of circulating tumor cells (CTCs) and the metastasis, which is a critical matter to improve patient management. PATIENTS AND METHODS: A retrospective series of 80 muscle-invasive primary bladder tumors and associated metastasis were screened for KRT14, 5, and 20 and STn by real-time polymerase chain reaction and immunohistochemistry. Peripheral blood was collected in a patients' subset, CTCs were isolated through a size-based microfluidic chip and screened for KRTs and STn. RESULTS: Basal-like lesions presented worse cancer-specific and disease-free survival compared to luminal tumors. STn antigen inclusion discriminated patients with worst survival in each subgroup (P = 0.047 for luminal; P = 0.027 for basal-like tumors). STn expression in CTCs and distant metastasis was also demonstrated. CONCLUSION: This work reinforces the potential of the KRT-based model for bladder cancer management and the association of STn with aggressiveness, supporting its inclusion in predictive molecular models toward patient-tailored precision medicine. Moreover, we describe for the first time that CTCs and the metastasis present a basal phenotype and express the STn antigen, highlighting its link with disease dissemination. Future studies should focus on determining the biological and clinical significance of these observations in the context of liquid biopsies. Given the membrane nature of STn, highly specific targeted therapeutics may also be envisaged.
OBJECTIVES: To evaluate the potential of sialyl-Tn (STn), a cancer-associated glycan antigen present in membrane glycoproteins, to improve a recent molecular model for stratification and prognostication of advanced stage bladder tumors based on keratins (KRT14, 5, and 20) expression. In addition, determine the association between STn and disease dissemination based on the evaluation of circulating tumor cells (CTCs) and the metastasis, which is a critical matter to improve patient management. PATIENTS AND METHODS: A retrospective series of 80 muscle-invasive primary bladder tumors and associated metastasis were screened for KRT14, 5, and 20 and STn by real-time polymerase chain reaction and immunohistochemistry. Peripheral blood was collected in a patients' subset, CTCs were isolated through a size-based microfluidic chip and screened for KRTs and STn. RESULTS: Basal-like lesions presented worse cancer-specific and disease-free survival compared to luminal tumors. STn antigen inclusion discriminated patients with worst survival in each subgroup (P = 0.047 for luminal; P = 0.027 for basal-like tumors). STn expression in CTCs and distant metastasis was also demonstrated. CONCLUSION: This work reinforces the potential of the KRT-based model for bladder cancer management and the association of STn with aggressiveness, supporting its inclusion in predictive molecular models toward patient-tailored precision medicine. Moreover, we describe for the first time that CTCs and the metastasis present a basal phenotype and express the STn antigen, highlighting its link with disease dissemination. Future studies should focus on determining the biological and clinical significance of these observations in the context of liquid biopsies. Given the membrane nature of STn, highly specific targeted therapeutics may also be envisaged.
Authors: Silvina Ribeiro-Samy; Marta I Oliveira; Thais Pereira-Veiga; Laura Muinelo-Romay; Sandra Carvalho; João Gaspar; Paulo P Freitas; Rafael López-López; Clotilde Costa; Lorena Diéguez Journal: Sci Rep Date: 2019-05-29 Impact factor: 4.379
Authors: Andreia Peixoto; Dylan Ferreira; Rita Azevedo; Rui Freitas; Elisabete Fernandes; Marta Relvas-Santos; Cristiana Gaiteiro; Janine Soares; Sofia Cotton; Beatriz Teixeira; Paula Paulo; Luís Lima; Carlos Palmeira; Gabriela Martins; Maria José Oliveira; André M N Silva; Lúcio Lara Santos; José Alexandre Ferreira Journal: J Exp Clin Cancer Res Date: 2021-06-09
Authors: Diana Canals Hernaez; Michael R Hughes; Pamela Dean; Peter Bergqvist; Ismael Samudio; Ola Blixt; Katharina Wiedemeyer; Yicong Li; Chris Bond; Eric Cruz; Martin Köbel; Blake Gilks; Calvin D Roskelley; Kelly M McNagny Journal: J Immunother Cancer Date: 2020-11 Impact factor: 13.751