An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors.

Purpose: The ability of vascular genes to provide treatment predictive information in breast cancer patients remains unclear. As such, we assessed the expression of genes representative of normal endothelial microvasculature (MV) in relation to treatment-specific patient subgroups.

Experimental Design: We used expression data from 993 breast tumors to assess 57 MV genes (summarized to yield an MV score) as well as the genomic grade index (GGI) and PAM50 signatures.

Multi-level gene expression signatures, but not binary, outperform Ki67 for the long term prognostication of breast cancer patients.

Proliferation-related gene signatures have been proposed to aid breast cancer management by providing reproducible prognostic and predictive information on a patient-by-patient basis. It is unclear however, whether a less demanding assessment of cell division rate (as determined in clinical setting by expression of Ki67) can function in place of gene profiling. We investigated agreement between literature-, distribution-based, as well as signature-derived values for Ki67, relative to the genomic grade index (GGI), 70-gene signature, p53 signature, recurrence score (RS), and the molecular subtype models of Sorlie, Hu, and Parker in representative sets of 253 and 159 breast cancers with a median follow-up of 13 and 14.

A simple method for assigning genomic grade to individual breast tumours.

Background: The prognostic value of grading in breast cancer can be increased with microarray technology, but proposed strategies are disadvantaged by the use of specific training data or parallel microscopic grading. Here, we investigate the performance of a method that uses no information outside the breast profile of interest.

Results: In 251 profiled tumours we optimised a method that achieves grading by comparing rank means for genes predictive of high and low grade biology; a simpler method that allows for truly independent estimation of accuracy.

Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration?

Mutations in PINK1 cause the mitochondrial-related neurodegenerative disease Parkinson's. Here we investigate whether obesity, type 2 diabetes, or inactivity alters transcription from the PINK1 locus. We utilized a cDNA-array and quantitative real-time PCR for gene expression analysis of muscle from healthy volunteers following physical inactivity, and muscle and adipose tissue from nonobese or obese subjects with normal glucose tolerance or type 2 diabetes.

Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.

Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models.

Comparative microarray analysis.

Microarrays enable high-throughput parallel gene expression analysis, and their use has grown exponentially during the past decade. We are now in a position where individual experiments could benefit from using the swelling public data repositories to allow microarrays to progress from being a hypothesis-generating tool to a powerful resource that can be used to test hypothesis about biology. Comparative microarray analysis could better distinguish phenotypes from associated phenotypes; identify valid differentially expressed genes by combining many studies; test new hypothesis; and discover fundamental patterns of gene regulation.

Gene expression in 16q is associated with survival and differs between Sørlie breast cancer subtypes.

We have investigated the relationship between gene expression and chromosomal positions in 402 breast cancer patients. Using an overrepresentation approach based on Fisher's exact test, we identified disproportionate contributions of specific chromosomal positions to genes associated with survival. Our major finding is that the gene expression in the long arm of chromosome 16 stands out in its relationship to survival.

The expression signature of in vitro senescence resembles mouse but not human aging.

Background: The biological mechanisms that underlie aging have not yet been fully identified. Senescence, a phenomenon occurring in vitro, limits the number of cell divisions in mammalian cell cultures and has been suggested to contribute to aging.

Results: We investigated whether the changes in gene expression that occur during mammalian aging and induction of cellular senescence are similar.