Glial cell proteome using targeted quantitative methods for potential multi-diagnostic biomarkers
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Published:2023-10-24
Issue:1
Volume:20
Page:
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ISSN:1542-6416
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Container-title:Clinical Proteomics
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language:en
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Short-container-title:Clin Proteom
Author:
Kang Narae,Oh Hyun Jeong,Hong Ji Hye,Moon Hyo Eun,Kim Yona,Lee Hyeon-Jeong,Min Hophil,Park Hyeonji,Lee Sang Hun,Peak Sun Ha,Jin Jonghwa
Abstract
AbstractGlioblastoma is one of the most malignant primary brain cancer. Despite surgical resection with modern technology followed by chemo-radiation therapy with temozolomide, resistance to the treatment and recurrence is common due to its aggressive and infiltrating nature of the tumor with high proliferation index. The median survival time of the patients with glioblastomas is less than 15 months. Till now there has been no report of molecular target specific for glioblastomas. Early diagnosis and development of molecular target specific for glioblastomas are essential for longer survival of the patients with glioblastomas. Development of biomarkers specific for glioblastomas is most important for early diagnosis, estimation of the prognosis, and molecular target therapy of glioblastomas. To that end, in this study, we have conducted a comprehensive proteome study using primary cells and tissues from patients with glioblastoma. In the discovery stage, we have identified 7429 glioblastoma-specific proteins, where 476 proteins were quantitated using Tandem Mass Tag (TMT) method; 228 and 248 proteins showed up and down-regulated pattern, respectively. In the validation stage (20 selected target proteins), we developed quantitative targeted method (MRM: Multiple reaction monitoring) using stable isotope standards (SIS) peptide. In this study, five proteins (CCT3, PCMT1, TKT, TOMM34, UBA1) showed the significantly different protein levels (t-test: p value ≤ 0.05, AUC ≥ 0.7) between control and cancer groups and the result of multiplex assay using logistic regression showed the 5-marker panel showed better sensitivity (0.80 and 0.90), specificity (0.92 and 1.00), error rate (10 and 2%), and AUC value (0.94 and 0.98) than the best single marker (TOMM34) in primary cells and tissues, respectively. Although we acknowledge that the model requires further validation in a large sample size, the 5 protein marker panel can be used as baseline data for the discovery of novel biomarkers of the glioblastoma.
Funder
Institute of Information & communications Technology Planning & Evaluation (IITP) grant
the National Research Foundation of Korea (NRF) grant funded by the Korea government
Korea University Grant
Bio & Medical Technology Development Program of the National Research Foundation
the National Research Foundation of Korea Grant
the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program
Electronics and Telecommunications Research Institute (ETRI) grant funded by the Korean government
Soonchunhyang University Research Fund; the National Research Foundation of Korea (NRF) grant funded by the Korea governmen
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Molecular Biology,Molecular Medicine,Clinical Biochemistry,Molecular Biology,Molecular Medicine
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