Cargando…

Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused...

Descripción completa

Detalles Bibliográficos
Autores principales: Kong, Ying, Chen, Hao, Chen, Mengyu, Li, Yongshuai, Li, Jiarong, Liu, Qi, Xiong, Huan, Guo, Tangxi, Xie, Yan, Yuan, Yufeng, Zhang, Xiao-Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980540/
https://www.ncbi.nlm.nih.gov/pubmed/35392238
http://dx.doi.org/10.3389/fonc.2022.855952
_version_ 1784681417484009472
author Kong, Ying
Chen, Hao
Chen, Mengyu
Li, Yongshuai
Li, Jiarong
Liu, Qi
Xiong, Huan
Guo, Tangxi
Xie, Yan
Yuan, Yufeng
Zhang, Xiao-Lian
author_facet Kong, Ying
Chen, Hao
Chen, Mengyu
Li, Yongshuai
Li, Jiarong
Liu, Qi
Xiong, Huan
Guo, Tangxi
Xie, Yan
Yuan, Yufeng
Zhang, Xiao-Lian
author_sort Kong, Ying
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.
format Online
Article
Text
id pubmed-8980540
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89805402022-04-06 Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis Kong, Ying Chen, Hao Chen, Mengyu Li, Yongshuai Li, Jiarong Liu, Qi Xiong, Huan Guo, Tangxi Xie, Yan Yuan, Yufeng Zhang, Xiao-Lian Front Oncol Oncology Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC. Frontiers Media S.A. 2022-03-22 /pmc/articles/PMC8980540/ /pubmed/35392238 http://dx.doi.org/10.3389/fonc.2022.855952 Text en Copyright © 2022 Kong, Chen, Chen, Li, Li, Liu, Xiong, Guo, Xie, Yuan and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kong, Ying
Chen, Hao
Chen, Mengyu
Li, Yongshuai
Li, Jiarong
Liu, Qi
Xiong, Huan
Guo, Tangxi
Xie, Yan
Yuan, Yufeng
Zhang, Xiao-Lian
Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title_full Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title_fullStr Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title_full_unstemmed Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title_short Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis
title_sort abnormal eca-binding membrane glycans and galactosylated cat and p4hb in lesion tissues as potential biomarkers for hepatocellular carcinoma diagnosis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980540/
https://www.ncbi.nlm.nih.gov/pubmed/35392238
http://dx.doi.org/10.3389/fonc.2022.855952
work_keys_str_mv AT kongying abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT chenhao abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT chenmengyu abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT liyongshuai abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT lijiarong abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT liuqi abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT xionghuan abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT guotangxi abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT xieyan abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT yuanyufeng abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis
AT zhangxiaolian abnormalecabindingmembraneglycansandgalactosylatedcatandp4hbinlesiontissuesaspotentialbiomarkersforhepatocellularcarcinomadiagnosis