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Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP

Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospita...

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Autores principales: Lee, Young-Sun, Ko, Eunjung, Yoon, Eileen L., Jung, Young Kul, Kim, Ji Hoon, Seo, Yeon Seok, Yim, Hyung Joon, Kim, Kyun-Hwan, Kwon, So Young, Yeon, Jong Eun, Um, Soon Ho, Byun, Kwan Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074125/
https://www.ncbi.nlm.nih.gov/pubmed/31979338
http://dx.doi.org/10.3390/jcm9020323
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author Lee, Young-Sun
Ko, Eunjung
Yoon, Eileen L.
Jung, Young Kul
Kim, Ji Hoon
Seo, Yeon Seok
Yim, Hyung Joon
Kim, Kyun-Hwan
Kwon, So Young
Yeon, Jong Eun
Um, Soon Ho
Byun, Kwan Soo
author_facet Lee, Young-Sun
Ko, Eunjung
Yoon, Eileen L.
Jung, Young Kul
Kim, Ji Hoon
Seo, Yeon Seok
Yim, Hyung Joon
Kim, Kyun-Hwan
Kwon, So Young
Yeon, Jong Eun
Um, Soon Ho
Byun, Kwan Soo
author_sort Lee, Young-Sun
collection PubMed
description Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.
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spelling pubmed-70741252020-03-19 Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP Lee, Young-Sun Ko, Eunjung Yoon, Eileen L. Jung, Young Kul Kim, Ji Hoon Seo, Yeon Seok Yim, Hyung Joon Kim, Kyun-Hwan Kwon, So Young Yeon, Jong Eun Um, Soon Ho Byun, Kwan Soo J Clin Med Article Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC. MDPI 2020-01-23 /pmc/articles/PMC7074125/ /pubmed/31979338 http://dx.doi.org/10.3390/jcm9020323 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Young-Sun
Ko, Eunjung
Yoon, Eileen L.
Jung, Young Kul
Kim, Ji Hoon
Seo, Yeon Seok
Yim, Hyung Joon
Kim, Kyun-Hwan
Kwon, So Young
Yeon, Jong Eun
Um, Soon Ho
Byun, Kwan Soo
Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title_full Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title_fullStr Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title_full_unstemmed Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title_short Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP
title_sort multiplexed proteomic approach for identification of serum biomarkers in hepatocellular carcinoma patients with normal afp
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074125/
https://www.ncbi.nlm.nih.gov/pubmed/31979338
http://dx.doi.org/10.3390/jcm9020323
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