Project description:Several molecular signatures are able to predict the activity of adjuvant chemotherapy in breast cancer patients. However, no molecular data are already available to detect microenvironment molecular signature that can identify patients who are good candidates for treatment with immune checkpoint inhibitors (ICIs). For this reason, in a series of women with operable high grade breast cancer (HGBC), we tried to combine the ECM3 and IFN molecular signatures reflecting different aspects of tumor microenvironment that can better draw the picture of the tumor microenvironment in which the immune cells are in close contact with extracellular matrix. Grade 3 primary tumors
Project description:Several molecular signatures are able to predict the activity of adjuvant chemotherapy in breast cancer patients. However, no molecular data are already available to detect microenvironment molecular signature that can identify patients who are good candidates for treatment with immune checkpoint inhibitors (ICIs). For this reason, in a series of women with operable high grade breast cancer (HGBC), we tried to combine the ECM3 and IFN molecular signatures reflecting different aspects of tumor microenvironment that can better draw the picture of the tumor microenvironment in which the immune cells are in close contact with extracellular matrix. Subgroup of G3 tumors extracted from the ECTO1 study (Gianni L. et al, JCO 2009)
Project description:Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors presenting a wide spectrum of different clinical and biological characteristics. In these tumors, the histological evaluation is a crucial element of clinical management. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, is the most reliable predictor of prognosis. This scoring method is time-consuming and a high reproducibility cannot be achieved. Novel approaches are needed to support histological evaluation and prognosis. In this study, starting from a microarray analysis, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. Moreover, we identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, we found miR-96-5p that raised its expression levels from grade 1 to grade 3; inversely, its target FOXO1 was decrease from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET correlates their expression with grading showing a potential advantage of miRNA quantification to aid clinicians in the classification of common GEP-NETs subtypes.
Project description:Breast cancer in women <40, accounting for ~5% of all breast cancer cases diagnosed in the U.S., is more aggressive and associated with worse outcomes compared to breast cancer in older women. We performed a first-ever integrated proteogenomic study from a matched cohort of laser-microdissected tumors of 34 young (<40 years) and 34 older (≥60 years) women to identify molecular features that may underlie the worse outcomes in young women. Progression-free interval was shorter in young women, and their tumors were enriched for more aggressive molecular subtypes. Our multi-omic analysis identified distinct clusters in luminal, but not basal-like cancers between age groups. Notably, GATA3 mutations were enriched in luminal tumors from young women, while TP53 and PIK3CA mutations more common in luminal tumors from older women. Young women’s tumors exhibited lower estrogen receptor (ER) expression yet paradoxically enhanced ER response pathways and increased expression of tamoxifen-resistance-associated genes (IRS1, FERMT1). Immune pathway activity and immune scores were lower in tumors from young women, whereas proliferative and MYC pathways were notably elevated, identifying potential therapeutic targets. Transcriptomic data from TCGA and METABRIC confirmed our findings, with 10 of 11 observed pathways corroborated. Finally, differential expression of four immune-related surface proteins also suggested potential age-specific responses of immune-based therapies. Together, these findings may contribute to the understanding of the molecular mechanisms underlying worse outcomes in young women, and offer new insight to therapeutic strategies.
Project description:Expression profile of human GEP-NET tumors, including 113 fresh frozen biopsies of primary and metastatic tumours originating from pancreas (P-NET, 83 primary and 30 metastasis), 81 from small intestine (SI-NET, 44 primary and 37 metastasis), and 18 from rectum (RE-NET, 3 primary and 15 metastasis).