Methodology and Applications of Disease Biomarker Identification in Human Serum

Abstract

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.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption-ionization timeof-flight mass spectrometry; MDLC, multidimensional liquid chromatography; MUC, mucin; MudPIT, multi-dimensional protein identifi cation technology; OA, osteoarthrosis; pI, isoelectric point; PSA, prostate-specific antigen; RA, rheumatoid arthritis; RP-HPLC, reversed-phased-high performance liquid chromatography; RPLC, reversed phase liquid chromatography; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; SEC, size exclusion chromatography; SELDI, surface-enhanced laser desorption ionization; SELDI-TOF, surface-enhanced laser desorption ionization-time of flight