Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival

Background

Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays.

Methods and Findings

Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment.

Conclusions

Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.     

Radio‐tags have no behavioral or physiological effects on a migratory songbird during breeding and molt

ABSTRACT Radio‐tags are commonly used in studies of avian behavior and ecology, even though many studies have revealed negative impacts of radio‐tags. Other studies of songbirds have revealed no negative effects of radio‐tags on parental care, nesting success, or annual return rates. However, such studies have not addressed the potential physiological costs of carrying radio‐tags or determined if such costs affect birds during the energetically costly molt period. Simultaneously investigating the behavioral, physiological, and fitness consequences of radio‐tags is important for evaluating possible costs. We studied Wood Thrushes (Hylocichla mustelina) in northwestern Pennsylvania and used a repeated‐measures design to determine if radio‐tags affected parental care behavior and nesting success, and measured levels of plasma lipid metabolites (β‐hydroxybutyrate, free glycerol, and triglycerides) to evaluate physiological condition. We also examined the possible physiological effects of radio‐tags during the energetically demanding period of molt in late summer. Radio‐tags did not affect male or female feeding rates, nesting success, number of nesting attempts, number of eggs laid, fledging success, or hatching success, and we found no significant effects of radio‐tag use on levels of plasma lipid metabolites of nesting females. During molt, Wood Thrushes with radio‐tags had lower levels of β‐hydroxybutyrate and higher levels of trigylcerides, suggesting they were in better, not worse, energetic condition. Our results suggest that radio‐tags do not have negative effects on the behavior or physiology of Wood Thrushes. Similar studies on a wider range of songbirds are needed before concluding radio‐tags have little or no impact during the molting period.     

Effects of cyclone waves on massive coral assemblages on the Great Barrier Reef: meteorology,hydrodynamics and demography

Cyclone waves directly affect the density, structure and local distribution of coral assemblages by acting as agents of mortality and colony transport. Using the meteorological record, hydrodynamic formulations and risk analysis, we predict some demographic consequences of cyclones for massive corals growing in different regions of the Great Barrier Reef. Analysis of shear, compression and tension forces generated by waves indicate that corals firmly attached to solid substratum, even if only over a small proportion of their base, can resist all waves, regardless of colony size or shape, cyclone intensity or region. Waves are thus directly important as controls on colony-size frequency distributions only for weakly attached or unattached colonies. At 3 m depth, these colonies have a higher probability of escaping dislodgement in their first 10 years of life, the further north or south they are from 21°S, which is the latitude where severe cyclones are most frequent. At 21°S, corals at depths as great as 12m are exposed to the greatest likelihood of dislodgement. Possible implications of predicted increased storminess associated with global warming are briefly discussed.