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MicroRNAs AS BIOMAKERS FOR THE IN VITRO DIAGNOSIS OF GLIOMA

Circulating microRNAsDigital PCR techniqueGliomas and glioblastomasMiR-487 MiR-26a-1 MiR-1

Introduction

Malignant gliomas, in particular glioblastomas, are associated with high morbidity, constituting a diagnostic-therapeutic challenge due to the aggressive and infiltrating behaviour. The absence of non-invasive biomarkers to monitor their growth, progression and response to therapies is a major problem in clinical practice, for which clinical studies and innovative molecular techniques are required.

Technical features

Gliomas are common and lethal brain tumors for which histological examination is still the most used diagnostic approach. The genetic/epigenetic peculiarity of tumors, however, challenges the approach. The diagnosis, to be completed, requires molecular evaluation. MiRNAs, small RNAs regulating gene expression, play a key role in physiological processes. Their alteration is associated with various diseases such as gliomas. They are stable molecules, detectable both in tissues and in biological liquids (serum and/or plasma), valid non-invasive biomarkers. However, a single miRNA, due to tumor multifactoriality, is an inaccurate biomarker. Evaluating a miRNA signature is a better approach for the complexity of tumors. The test analyzes, starting from a blood sample collected before surgery, the expression of 3 circulating miRNAs belonging to a signature of 10, whose combination (miR-487 / miR-26a-1 / miR-1) discriminates with specificity patients with IDH1 mutations from patients with wild-type (not mutated) genotype. Samples are processed within 4 hours of collection. The analysis of the expression of the signature is carried out by digital PCR which quantifies the analyte through a mixture of sample dilution and the Poisson algorithm.

Possible Applications

  • Use of specific serum miRNA signatures that can be analyzed by liquid biopsy that offer complementary information with respect to histological, molecular and imaging techniques. They provide concrete diagnostic/prognostic help and are adopted for a personalized clinical approach.

Advantages

  • Non-invasive, quick and inexpensive test;
  • Improvement of diagnostic and prognostic accuracy;
  • Liquid biopsies that facilitate serial sampling and monitoring of the dynamic changes of tumors during the course of therapies.