S100PROTEINS IN BREAST CANCER: MULTIOMICS-BASED ANALYSIS

Abstract

S100 gene family is the largest subfamily of calcium binding proteins, expressed in tissue and cell-specific manner. Within cells, S100 have been involved in the regulation of proliferation, differentiation, apoptosis, energy metabolism, inflammation, migration and invasion. Extracellular S100 proteins act in an autocrine and paracrine manner and regulate cell proliferation, differentiation, survival and migration. S100 proteins play important roles in the development and progression of tumors due to their multifunctional roles. However, the occurrence, the role and the possible coordination of this group of proteins in breast cancer is still poorly known. We previously describe a large-scale proteomic investigation performed on breast cancer patients for the screening of multiple forms of S100 proteins1,2. Our results have shown that the majority of S100 proteins are preferentially expressed in the tumor mass compared with the normal adjacent tissue and that some S100 protein members were ubiquitously expressed in almost all patients, while others appeared more sporadic among the same group of patients. More interestingly, patients which developed distant metastases showed a general tendency of higher S100 protein expression, compared to the disease-free group. Present study was aimed to assess the gene expression levels of the S100 protein family members utilizing a breast cancer dataset generated on Affymetrix microarrays technologies3. GOBO (Gene expression-based Outcome for Breast cancer Online) is a user-friendly online tool that allows, also, the identification of co-expressed genes and association with outcome in an 1881 breast cancer samples. Other important association with breast cancer outome was carried out by Kaplan Meir-plotter database4. Integrating results obtained by proteomic and trascriptomic analysis of S100 proteins highlight their important involvement in breast cancer progression. Future studies are needed to disclose molecular mechanisms and signaling pathways that define the multiple and specific roles of S100 proteins in breast cancer.