Innovative methodology for the identification of soluble biomarkers in fresh tissues

// Brunella Costanza 1, * , Andrei Turtoi 1, * , Akeila Bellahcene 1 , Touko Hirano 2 , Olivier Peulen 1 , Arnaud Blomme 1 , Vincent Hennequiere 1 , Eugene Mutijima 3 , Jacques Boniver 3 , Marie-Alice Meuwis 4 , Claire Josse 5 , Benjamin Koopmansch 5 , Karin Segers 5 , Takehiko Yokobori 6 , Karim Fahmy 1 , Marc Thiry 7 , Carla Coimbra 8 , Nancy Garbacki 9 , Alain Colige 9 , Dominique Baiwir 10, 11 , Vincent Bours 5 , Edouard Louis 4 , Olivier Detry 8 , Philippe Delvenne 3 , Masahiko Nishiyama 6, 12 and Vincent Castronovo 1 1 Metastasis Research Laboratory, GIGA Cancer, University of Liege, Liege, Belgium 2 Laboratory for Analytical Instruments, Gunma University Graduate School of Medicine, Gunma, Japan 3 Department of Pathology, University Hospital (CHU), University of Liege, Liege, Belgium 4 Gastroenterology Department, University Hospital (CHU), University of Liege, Liege, Belgium 5 Center for Human Genetic, Molecular Haemato-Oncology Unit, UniLab, University Hospital (CHU), University of Liege, Liege, Belgium 6 Division of Integrated Oncology Research, Research Program for Omics-based Medical Science, Gunma University Initiative for Advanced Research, Gunma, Japan 7 Laboratory of Cell Biology, Faculty of Sciences, University of Liege, Liege, Belgium 8 Department of Abdominal Surgery, University Hospital (CHU), University of Liege, Liege, Belgium 9 Laboratory of Connective Tissues Biology, GIGA-Cancer, University Hospital, University of Liege, Liege, Belgium 10 Mass Spectrometry Laboratory, University of Liege, Liege, Belgium 11 GIGA Proteomics Facility, University of Liege, Liege, Belgium 12 Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Gunma, Japan * These authors have contributed equally to this work Correspondence to: Vincent Castronovo, email: vcastronovo@ulg.ac.be Keywords: biomarkers; proteomic; miRNAs; tDNA; metabolomic Received: August 05, 2017     Accepted: January 19, 2018     Published: January 31, 2018 ABSTRACT The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure named EXPEL that uses rapid, pressure-assisted, interstitial fluid extrusion, preserving the specimen for full routine clinical pathology investigation. In the meantime, the technique allows a comprehensive OMICs analysis (proteins, metabolites, miRNAs and DNA). As proof of concept, we have applied EXPEL on freshly collected human colorectal cancer and liver metastases tissues. We demonstrate that the procedure efficiently allows the extraction, within a few minutes, of a wide variety of biomolecules holding diagnostic and prognostic potential while keeping both tissue morphology and antigenicity unaltered. Our method enables, for the first time, both clinicians and scientists to explore identical clinical material regardless of its origin and size, which has a major positive impact on translation to the clinic.