Cover Picture: Proteomics – Clinical Applications 11/09

AbstractBop‐a‐hepcidinThe appropriate level of iron in a cell is critical to its health: too much and you have hereditary hemochromatosis; too little and it's iron deficiency anemia. Hepcidin‐25, expressed in the liver, appears to be the principal homeostatic regulator of iron although two other forms of hepcidin are known, hepcidin‐20 and hepcidin‐22. Their function(s) have not been explicated, possibly they are antibacterial. Complicating matters further, up‐ and down‐regulation of the various hepcidins are not regulated synchronously in various cell lines and primary hepatocyte cultures. To get a grip on this confusion, Hosoki et al. developed a protocol to simultaneously determine the concentration of the three hepcidin isotypes. Using stable isotope‐labeled hepcidin‐22, ‐25 as internal standards and Q‐TOF/MS, very good accuracy and simultaneous determination is achieved. They also found that fetal calf serum has substantial but variable levels of an unknown up‐regulator of hepcidin and requires careful consideration when interpreting experimental results.Hosoki, T. et al., Proteomics Clin. Appl. 2009, 3, 1256–1264.Slurpy sample shows fingerprint of fibromyalgiaThe multitude of symptoms that might be presented by fibromyalgia (FM) is imposing. Widespread pain might be accompanied by any of nearly a dozen features, including fatigue, specific tenderness points, anxiety, depression, autonomic complaints such as irritable bladder or bowel, and so on. Various autoantibodies, specific and nonspecific, have been frequently found in patient sera, but have never shown signs of inflammation. Given the diversity of symptoms, Bazzichi et al. decided to apply 2‐D PAGE, MALDI TOF/TOF and MS/MS to whole saliva in search of suitable biomarkers for FM. They confirmed the upregulation of transaldolase, an enzyme in the pentose phosphate pathway, and phosphoglycerate mutase 1. Other proteins that exhibited clear shifts in the expression levels included gelsolin, profilin, cofilin, rho GDP dissociation inhibitor 2, proteasome subunit α type‐2, and haptoglobin‐related protein precursor.Bazzichi, L. et al., Proteomics Clin. Appl. 2009, 3, 1296–1304.A breast cancer is not just another breast cancerBreast cancer is now subdivided into five subtypes: Luminal type A, Luminal type B, HER2+, Basal and Normal‐like. So, how different are they? Well, HER2+ and luminal type A give a patient about a 95% chance of surviving 5 years versus 50% for luminal type B. These differ by the level of expression of estrogen receptor α (ERα). Genomic tests generally yield good discrimination, but can be confounded by mutations that are not a problem for proteomic tests. Nakshatri et al. examined the proteomes of plasma from luminal A, luminal B, HER2+ and basal versus normal patients looking at the expression of ERα, progesterone receptor (PR, not expressed in luminal B) and HER2. Subtypes can be reliably distinguished, but questions remain on the relationship of luminal A and B.Nakshatri, H. et al., Proteomics Clin. Appl. 2009, 3, 1305–1313.