Functional proteomics outlines the complexity of breast cancer molecular subtypes

Breast cancer is a heterogeneous disease comprising a variety of entities with various genetic backgrounds. Estrogen receptor-positive, human epidermal growth factor receptor 2-negative tumors typically have a favorable outcome; however, some patients eventually relapse, which suggests some heterogeneity within this category. In the present study, we used proteomics and miRNA profiling techniques to characterize a set of 102 either estrogen receptor-positive (ER+)/progesterone receptorpositive (PR+) or triple-negative formalin-fixed, paraffin-embedded breast tumors. Protein expressionbased probabilistic graphical models and flux balance analyses revealed that some ER+/PR+ samples had a protein expression profile similar to that of triple-negative samples and had a clinical outcome similar to those with triple-negative disease. This probabilistic graphical model-based classification had prognostic value in patients with luminal A breast cancer. This prognostic information was independent of that provided by standard genomic tests for breast cancer, such as MammaPrint, OncoType Dx and the 8-gene Score

miRNA profiling in renal carcinoma suggest the existence of a group of pro-angionenic tumors in localized clear cell renal carcinoma.

Renal cell carcinoma comprises a variety of entities, the most common being the clear-cell, papillary and chromophobe subtypes. These subtypes are related to different clinical evolution; however, most therapies have been developed for clear-cell carcinoma and there is not a specific treatment based on different subtypes. In this study, one hundred and sixty-four paraffin samples from primary nephrectomies for localized tumors were analyzed. MiRNAs were isolated and measured by microRNA arrays. Significance Analysis of Microarrays and Consensus Cluster algorithm were used to characterize different renal subtypes. The analyses showed that chromophobe renal tumors are a homogeneous group characterized by an overexpression of miR 1229, miR 10a, miR 182, miR 1208, miR 222, miR 221, miR 891b, miR 629-5p and miR 221-5p. On the other hand, clear cell renal carcinomas presented two different groups inside this histological subtype, with differences in miRNAs that regulate focal adhesion, transcription, apoptosis and angiogenesis processes. Specifically, one of the defined groups had an overexpression of proangiogenic microRNAs miR185, miR126 and miR130a. In conclusion, differences in miRNA expression profiles between histological renal subtypes were established. In addition, clear cell renal carcinomas had different expression of proangiogenic miRNAs. With the emergence of antiangiogenic drugs, these differences could be used as therapeutic targets in the future or as a selection method for tailoring personalized treatments