Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.

Our findings suggest that multiple BDNF-TrkB signaling pathways are activated in HH. They act independently or collaboratively to downregulate KCC2 expression, which is the key component for GABA-mediated excitation associated with gelastic seizures.

Ductal carcinoma in situ represents an earliest identifiable breast cancer lesion. The disruption of the myoepithelial cell layer and basement membrane is a prerequisite for DCIS to initiate invasion into the stroma. The majority of epithelial cells overlying a focally disrupted myoepithelial cell layer are estrogen receptor-alpha negative, or ER(-); however, adjacent cells within the same duct confined by an intact myoepithelial cell layer express high levels of ER. These ER (+) and ER (-) cells were microdissected from the same ducts of breast cancer patients. Differential proteins expressed by ER(+) and ER(-) cells were identified using two-dimensional gel electrophoresis followed by mass spectrometry and Western blot analysis. ER(-) cells express lower levels of superoxide dismutase, Ral A protein, galectin-1, uridine phosphorylase, cellular retinoic acid-binding protein 1, S100 calcium binding protein A11, and nucleoside diphosphate kinase A or non-metastasis protein 23-H1 (nm23-H1). The upregulated protein, Rho GDP-Dissociation Inhibitor 1 alpha, may induce chemotherapy resistance. The significant findings are that the microdissected ER(-) cells express 13.5 times less cellular retinoic acid-binding protein 1, a protein involved in cellular differentiation, and 34.2 times less nucleoside diphosphate kinase A or (nm23-H1), a metastasis suppressor, and express fewer proteins than adjacent ER(+) cells. The collective role of the alteration of protein expression in ER(-) cells may be promoting a more malignant phenotype than adjacent ER(+) cells, including decreased ability to undergo apoptosis and differentiation, and increased potential to damage DNA, metastasize, and resist chemotherapy.

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