Identificazione di biomarcatori prognostici nel siero di pazienti con sarcoma mediante analisi proteomica

Soft Tissue Sarcomas (STS) are rare tumors with troubles in diagnosis and prognosis. Recently, development of "high throughput screening" techniques has allowed to carry out investigations about molecular background of the individual patient's tumor, providing data for selection of biomarkers with significant clinical impact. The identification of new circulating biomarkers is crucial for early diagnosis, for stratification of high-risk patients and for monitoring the progression or response to therapy. A new totally non-invasive nanotechnology has been used in this study. The †˜core-shell hydrogel nanoparticles', in fact, excluding very abundant serum proteins can bind and concentrate peptide fragments or low molecular weight proteins, released by tumor cells and tissues, present in serum in so poor concentration as not to be detectable with the conventional immunological techniques. The validation of these identified proteins was carried out on another set of sera from patients with Soft Tissue Sarcomas by ELISA, that showed median IGFBP7 level significantly higher in STS when compared to controls, providing a threshold value of 25ng/ml to distinguish tumor from non-tumor patients. Since circulating molecules derived from protein fragments that are in tumor microenvironment, tissue analysis of IGFBP7 with IHC on a larger number of samples has detected a higher intensity of staining in metastatic rather than in non-metastatic tumors, with IGFBP7 as an independent biomarker of poor prognosis. Finally, expression analysis of 12 miRNA, involved in tumor development and progression, with validation of miR-152 downregulation and subsequent overexpression of its targets MET and KIT, opens the way for future integration of molecular profile studies looking for specific potential "targets" for future clinical-therapeutic personalized applications.