Project description:This study identifies miR-138 as a prognostic biomarker for basal breast carcinoma. Identification of differentially regulated genes upon miR-138 knockdown (AntagomiR-138) in basal breast cancer cell lines MDA-MB-231
Project description:Triple negative breast cancer (TNBC) accounts for 15-20% of all breast carcinomas and it is clinically characterized by an aggressive phenotype and bad prognosis. TNBC does not benefit from any targeted therapy, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of one hundred twenty-five formalin-fixed paraffin-embedded samples from patients diagnosed with triple negative breast cancer were analyzed by mass spectrometry using data-independent acquisition. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were used to characterize molecular groups. Additionally, a predictive signature related with relapse was defined. Two molecular groups with differences in several biological processes as glycolysis, translation and immune response, were defined in this cohort, and a prognostic signature based on the abundance of proteins RBM3 and NIPSNAP1 was defined. This predictor split the population into low-risk and high-risk groups. The differential processes identified between the two molecular groups may serve to design new therapeutic strategies in the future and the prognostic signature could be useful to identify a population at high-risk of relapse that could be directed to clinical trials.
Project description:Medullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
Project description:Gene Expression Profiling of Primary Male Breast Cancers Reveals Two Unique Subgroups and Identifies N-acetyltransferase-1 (NAT1) as a Novel Prognostic Biomarker
Project description:Medullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative. The IPC series contained frozen tumor samples obtained from 266 early breast cancer patients who underwent initial surgery in our institution between 1992 and 2004. They included 227 cases previously reported {Finetti, 2008 #1758} and 39 additional cases, all similarly profiled using Affymetrix U133 Plus 2.0 human oligonucleotide microarrays as previously described {Finetti, 2008 #1758}. The study was approved by the IPC review board, and informed consent was available for each case. Gene expression data of 266 BCs were quantified by using whole-genome DNA microarrays (HG-U133 plus 2.0, Affymetrix).