Prospective validation of the prognostic/predictive value of several markers

LABORATORY OF EXPERIMENTAL ONCOLOGY Rizzoli Orthopedic Institute, Bologna, Italy

In the years the Laboratory of Experimental Oncology at the Rizzoli Institute has specialized in translational research of musculoskeletal sarcomas and in optimizing multidisciplinary treatments. Molecular characterization of musculoskeletal sarcomas is aimed at the identification of genetic and/or protein biomarkers correlated to the state of the disease, with a relevant clinical impact for diagnostic, prognostic and therapeutic implications.

AIM OF THE PROJECT
Rizzoli Institute group contributes to Provabes project with the validation of prognostically relevant biomarkers of Ewing’s sarcoma. In particular, MGST1, the microsomial gluthatione transferase, miR34a and GALS3BP, lectin galactoside-binding soluble 3 binding protein, expression will be analyzed and validated as indicators of differential clinical outcome. Our primary aims will be the validation in a prospective series of patients of the mentioned biomarkers, together with the definition (exploratory phase) of their molecular mechanisms. Expression in the tumors will be correlated with their expression in the plasma of patients. Definition of the best standardize procedures to establish evaluation of miRNA/mRNA is a mandatory step to define the value to liquid biopsies also in the Ewing’s sarcoma patients.

WORKPLAN
Prospective validation of the prognostic/predictive value of
MGST1: HGCN 7061 4257 (microsomal glutathione S-transferase 1),
hsa-mir-34a: HGCN 31635 4070 40 (microRNA 34a, miR34a)- expression and
LGALBP3: HGCN 6564 3959 (lectin, galactose binding soluble, 3 binding protein)
expression in ES samples.
Assay validation: Real time PCR (calibration) in cooperation with ►WP5.
In situ hybridisation of hsa-mir-34a on paraffin material.
Expression of miR34 in body fluids in cooperation with ►WP5
Cross validation with exome and RNA sequencing (►WP 1.2) and protein expression (►WP 3).
Exploratory: hsa-mir-34a, MGST1 and LGALS3BP expression as clinical marker: analysis of hsa-mir-34a, MGST1 and LGALS3BP expression in tumour and patient serum before and after chemotherapy treatments and correlation with clinical and histological response in cooperation with ►P.
Interaction of hsa-mir-34a LGALS3BPand p53/MGST1 in cooperation with ►WP 4 and ►P.