As shown in our resultsall classification methods achieved very good results. However, as reported in several studies, SVM and predictive methods have some limitations, since they could lead to too optimistic statement. Meyer et al.compared SVM to several other classification and regression methods, by means of standard performance measures. This comparison showed that all predictive methods have good performances, and SVM did not demonstrate its overall superiority. Parikesit et al.and Smith et al.assessed different predictive methods applied to gene annotations, and reported that predictions should be chosen carefully in order to avoid introducing biases. Although validation is necessary in independent wet lab experiments, the new genomic features identified in our work shed new light on the biology underlying histological grade in breast cancer, as evidenced in the following section. Among its possible Cinoxacin target genes, clusterinis a pro-proliferative gene and one of the genes induced by exposure to ionizing radiation, which usually causes oxidative damage, while neurobeachin, a lysosomal-trafficking regulator, is one of the genes of the common fragile site regions. Class 1 comprises also Hsa-miR-515-5p, that is usually down-regulated by estrogen receptor in BC. In our case this miRNA in unexpectedly up-regulated; this may possibly due to the fact that our database contains both ER+ and ER- BC samples. Hsa-miR-515-5p regulates a growth factor signalling transducer, the ring finger protein-like 1, which has a role in growth control of BC cell line. In class 1 we found also Hsa-miR-142-3p, that, with Hsa-miR-532-5p, is a circulating miRNA already considered biomarker of colorectal carcinoma. Two possible targets of this miRNAs are fibronectin type III domain containing 3A, whose expression controls cell adhesion, migration and proliferationand myotubularin related protein 9, whose chromosomal gain is considered a prognostic event in oesophageal adenocarcinoma. The last gene is also a possible target of Hsa-miR-941, that is a circulating biomarker of ulcerative colitis. Hsa-miR-455-5p has already been found to be up-regulated in different types of tumors, as basal cell carcinoma of the skin, endometrial adenocarcinomas, but it also has a diagnostic value in laryngeal cancerand in hepatocellular adenoma. Its target tight junction protein 1, being a protein of the cytoplasmic membrane surface of intracellular tight junction, could have a role in communication among two cells by cell-cell junction. A role for TJP1 in controlling epithelial cell integrity in BC cells has been pointed out. It is not a coincidence to find in G3 BC several upregulated miRNAs common to melanoma, as Axelsen JB et al.reported that the genes selectively altered in BC majorly overlap with the ones altered in melanoma. A combination of genetic and epigenetic Anemarsaponin-BIII changes has been shown to contribute to development of human cancer resulting in deregulation of gene expression and function. Genetic changes result in widespread deregulation of gene expression profiles and the disruption of signaling networks that control normal cell proliferation and functions. In addition to changes in DNA and chromosomes, oncogenic processes can be profoundly influenced by epigenetic mechanisms.