6 research outputs found
Analysis of Autoantibody Profiles in Osteoarthritis Using Comprehensive Protein Array Concepts
Osteoarthritis
(OA) is the most common rheumatic disease and one
of the most disabling pathologies worldwide. To date, the diagnostic
methods of OA are very limited, and there are no available medications
capable of halting its characteristic cartilage degeneration. Therefore,
there is a significant interest in new biomarkers useful for the early
diagnosis, prognosis, and therapeutic monitoring. In the recent years,
protein microarrays have emerged as a powerful proteomic tool to search
for new biomarkers. In this study, we have used two concepts for generating
protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable
protein arrays), to characterize differential autoantibody profiles
in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy
controls. An untargeted screen was performed on 3840 protein fragments
spotted on planar antigen arrays, and 373 antigens were selected for
validation on bead-based arrays. In the NAPPA approach, a targeted
screening was performed on 80 preselected proteins. The autoantibody
targeting CHST14 was validated by ELISA in the same set of patients.
Altogether, nine and seven disease related autoantibody target candidates
were identified, and this work demonstrates a combination of these
two array concepts for biomarker discovery and their usefulness for
characterizing disease-specific autoantibody profiles
Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer
<div><p>Background</p><p>Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.</p><p>Design/Subjects</p><p>Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.</p><p>Results</p><p>Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.</p><p>Conclusions</p><p>In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.</p></div
Correlations between CNDP1 and clinical parameters in cohort 2.
<p>Correlations were performed using simple linear regression, r- and p-values are shown.</p><p>Correlations between CNDP1 and clinical parameters in cohort 2.</p
Candidates found in the unbiased proteomic screen.
<p>Candidates found in the unbiased proteomic screen.</p
Clinical characteristics of cohort 1 and 2.
<p>Values are given as mean±S.D. except for gender where the actual number of males (M) and females (F) are given. Group values were compared using unpaired t-test or χ<sup>2</sup> test.</p><p>*Measured by bioimpedance in cohort 1 and by DXA in cohort 2.</p><p>Clinical characteristics of cohort 1 and 2.</p
Identification and validation of CNPD1 reduction in CC.
<p>Detected protein levels are shown for <b>A.</b> the screen using Sandwich Bead Arrays (SBA) and <b>B.</b> validation by Sandwich Immunoassays (SIA) and expressed as mean intensity fluorescence (MIF). <b>C.</b> There was an excellent correlation between results obtained by SBA and SIA. CNPD1 levels measured by SIA were not influenced by <b>D.</b> age or <b>E.</b> gender. <b>F.</b> Distribution of circulating CNDP1 concentrations determined by SIA in Cohort 2. WS = Weight stable, CC = Cancer cachexia. P- and rho-values are given.</p