Investigation of genetic variants of α-1 acid glycoprotein by ultra-performance liquid chromatography–mass spectrometry

Abstract

Genetic variants of human plasma alpha-1 acid glycoprotein (AGP) have been studied in cancer, compared with a group of healthy control. AGP has four genetic variants: AGP F1, F2, and S variants correspond to the ORM1 gene whereas AGP A corresponds to the ORM2 gene. The proportion of ORM1 and ORM2 variants were studied in plasma using a novel UPLC-MS method. Plasma total AGP level was 0.5 +/- 0.2 g L(-1) and the proportions of the ORM1 and ORM2 variants were 76.3 +/- 8.2% and 23.7 +/- 8.2%, respectively. In cancer plasma AGP levels increased fourfold and the proportion of ORM1 variants increased to 88.7 +/- 6.8%. Changes in the proportion of genetic variants due to cancer were clearly significant, as shown by statistical analysis. Three different cancer types have been studied, lymphoma, melanoma, and ovarian cancer. The results did not show any difference depending on cancer type. The results indicate that, in accordance with prior expectations, the ORM1 variant is predominantly responsible for the acute-phase property of AGP.

Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms

“…The molar ratio of the F1*S and A variants in blood typically ranges from 3:1 to 2:1 (8,9). However, Vékey and coworkers (10) reported that, in plasma of some cancer patients, AGP levels were increased by 4-fold and that the molar ratio of the F1*S and A variants was in the vicinity of 8:1. Therefore, the pharmacokinetics and pharmacodynamics of drugs that bind to hAGP are affected during inflammation not only as the result of increased hAGP concentrations but also by the change in the ratio of the hAGP variants.…”

Towards an Animal Model of Ovarian Cancer: Cataloging Chicken Blood Proteins Using Combinatorial Peptide Ligand Libraries Coupled with Shotgun Proteomic Analysis for Translational Research

“…Another example is creatine kinase B, which has been found to be upregulated in ovarian cancer cells in vitro and in vivo, and its enzyme activity is significantly elevated in sera from ovarian cancer patients (Huddleston et al, 2005). We also identified potential low-abundance biomarkers such as alpha-1 acid glycoprotein (Imre et al, 2008;Budai et al, 2009) (average PSM of 4.5), cysteine endopeptidases calpain (average PSM of 0.5) (Salehin et al, 2012), SPARC ( Mok et al, 1996, Said et al, 2008Chen et al, 2012) (average PSM of 1.5), tetranectin (average PSM of 8.17) (Hogdall et al, 1993, Hogdall et al, 1994Deng et al, 2000;Begum et al, 2009Begum et al, , 2010, and periostin (Zhu et al, 2010;Morra and Moch, 2011) (average PSM of 4.5) in chicken serum, and peroxiredoxin-1 (average PSM of 2) (Hoskins et al, 2011) in chicken plasma in this study. Therefore, our dataset provides many potential ovarian cancer biomarkers that await validation using MRM-based targeted proteomics because no antibodies to these proteins are available.…”

Under-Updated Particle Swarm Optimization for Small Feature Selection Subsets from Large-Scale Datasets

“…However, in the BC dataset, LAMB3 seems to be less expressed in metastatic tumors. ORM1 is increased in the plasma of cancer patients (Budai et al, 2009). This concurs in the BC dataset where the expression of ORM1 appears to be increased in metastatic tumors.…”