Individualized markers optimize class prediction of microarray data

BACKGROUND: Identification of molecular markers for the classification of microarray data is a challenging task. Despite the evident dissimilarity in various characteristics of biological samples belonging to the same category, most of the marker – selection and classification methods do not consider this variability. In general, feature selection methods aim at identifying a common set of genes whose combined expression profiles can accurately predict the category of all samples. Here, we argue that this simplified approach is often unable to capture the complexity of a disease phenotype and we propose an alternative method that takes into account the individuality of each patient-sample. RESULTS: Instead of using the same features for the classification of all samples, the proposed technique starts by creating a pool of informative gene-features. For each sample, the method selects a subset of these features whose expression profiles are most likely to accurately predict the sample's category. Different subsets are utilized for different samples and the outcomes are combined in a hierarchical framework for the classification of all samples. Moreover, this approach can innately identify subgroups of samples within a given class which share common feature sets thus highlighting the effect of individuality on gene expression. CONCLUSION: In addition to high classification accuracy, the proposed method offers a more individualized approach for the identification of biological markers, which may help in better understanding the molecular background of a disease and emphasize the need for more flexible medical interventions

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors.

We describe a new mechanism regulating the tumor endothelial barrier and T cell infiltration into tumors. We detected selective expression of the death mediator Fas ligand (FasL, also called CD95L) in the vasculature of human and mouse solid tumors but not in normal vasculature. In these tumors, FasL expression was associated with scarce CD8(+) infiltration and a predominance of FoxP3(+) T regulatory (Treg) cells. Tumor-derived vascular endothelial growth factor A (VEGF-A), interleukin 10 (IL-10) and prostaglandin E2 (PGE2) cooperatively induced FasL expression in endothelial cells, which acquired the ability to kill effector CD8(+) T cells but not Treg cells because of higher levels of c-FLIP expression in Treg cells. In mice, genetic or pharmacologic suppression of FasL produced a substantial increase in the influx of tumor-rejecting CD8(+) over FoxP3(+) T cells. Pharmacologic inhibition of VEGF and PGE2 produced a marked increase in the influx of tumor-rejecting CD8(+) over FoxP3(+) T cells that was dependent on attenuation of FasL expression and led to CD8-dependent tumor growth suppression. Thus, tumor paracrine mechanisms establish a tumor endothelial death barrier, which has a critical role in establishing immune tolerance and determining the fate of tumors