| Summary: | 碩士 === 國立臺灣大學 === 化學研究所 === 99 === Differential expression of disease-related biomarkers is the most common measure for early detection of disease, for monitoring effects of therapy, for detecting disease recurrence and for prognosis. Significant overexpression of plasma protein in cancer has received increasing attention in disease diagnosis. In addition to quantitative alterations in expression levels, genetic variations and post-translational modifications (PTMs) of proteins are also associated with disease states. Serum amyloid A (SAA), a major acute-phase protein, has received increasing attention due to its close association with inflammation. In previous reports, the expression of serum amyloid A (SAA) has been shown to be highly related to several diseases, especially cancer. However, the correlation of SAA variants with cancers has not been evaluated systematically.
Taking advantage of efficient affinity extraction by antibody-functionalized magnetic nanoparticles (MNPs) and accurate MALDI-TOF MS readout, we present a nanoprobe-based immunoassay for simultaneous isolation and screening of protein isoforms from human plasma. Relative quantification of these variants was performed by the addition of internal standard. Our results demonstrate that total 24 variants of SAA including SAA 1- and SAA 2- encoded protein products and their polymorphic isoforms, N-terminal truncated forms and three previously unidentified were identified from normal controls (n = 35), gastritis patients (n = 35), gastric cancer patients (n = 70), colon cancer patients (n = 61), and CADASIL patients (n = 31). Coupled with the bioinformatics study, we developed a computational model for cancer discrimination. In the gastric cancer study, the SAA variant pattern demonstrated discrimination of patients with gastric cancer from patients with gastritis or healthy subjects with sensitivity of 0.76 and specificity of 0.81. In the colon cancer study, the performance of SAA variant pattern has specificity of 0.69 and specificity of 0.82. However, the of SAA variants pattern did not show discrimination power in CADASIL study, which may indicate the SAA variants are highly related to malignant tumor-associated diseases.
|
|---|
