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.

Highlights

  • Biomarkers readily detectable in liquid biopsies are of utmost importance for any healthcare system, in particular for diagnostic and therapeutic applications

  • 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

  • Biomarker discovery is a crucial step for cancer early diagnosis, prognosis and prediction of therapy response

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Summary

Introduction

Biomarkers readily detectable in liquid biopsies are of utmost importance for any healthcare system, in particular for diagnostic and therapeutic applications. The use of liquid biopsies (e.g. serum, urine, saliva) brought the promise to circumvent this problem, opening access to many different entities like circulating DNA, exosomes (containing miRNAs), proteins and metabolites. Upon their release from the tumour these molecules are diluted up to several billion-fold in blood where they are mixed with species originating from healthy tissues. A “blanket of noise” precludes straightforward analysis and even detection of relevant molecules, covering the biomarkers that would be useful in diagnosing and understanding the disease

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