A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer

Lymph node metastasis (LNM) of colorectal cancer (CRC) is an important factor for both prognosis and treatment. Given the deficiencies of conventional tests, we aim to discover novel DNA methylation markers to efficiently identify LNM status of CRC. In this study, genome-wide methylation sequencing...

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Main Authors: Yingdian Yu, Wenyuan Xue, Zefeng Liu, Shang Chen, Jun Wang, Quanzhou Peng, Linhao Xu, Xin Liu, Chunhui Cui, Jian-Bing Fan
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1000823/full
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author Yingdian Yu
Wenyuan Xue
Zefeng Liu
Shang Chen
Jun Wang
Quanzhou Peng
Linhao Xu
Xin Liu
Chunhui Cui
Jian-Bing Fan
Jian-Bing Fan
Jian-Bing Fan
author_facet Yingdian Yu
Wenyuan Xue
Zefeng Liu
Shang Chen
Jun Wang
Quanzhou Peng
Linhao Xu
Xin Liu
Chunhui Cui
Jian-Bing Fan
Jian-Bing Fan
Jian-Bing Fan
author_sort Yingdian Yu
collection DOAJ
description Lymph node metastasis (LNM) of colorectal cancer (CRC) is an important factor for both prognosis and treatment. Given the deficiencies of conventional tests, we aim to discover novel DNA methylation markers to efficiently identify LNM status of CRC. In this study, genome-wide methylation sequencing was performed in a cohort (n=30) using fresh CRC tissue to discover differentially methylated markers. These markers were subsequently validated with fluorescence quantitative PCR in a cohort (n=221), and the optimal marker was compared to conventional diagnostic methods. Meanwhile, immunohistochemistry was used to verify the effectiveness of the antibody corresponding to this marker in a cohort (n=56). LBX2 achieved an AUC of 0.87, specificity of 87.3%, sensitivity of 75.7%, and accuracy of 81.9%, which outperformed conventional methods including imaging (CT, PET-CT) with an AUC of 0.52, CA199 with an AUC of 0.58, CEA with an AUC of 0.56. LBX2 was also superior to clinicopathological indicators including the depth of tumor invasion and lymphatic invasion with an AUC of 0.61and 0.63 respectively. Moreover, the AUC of LBX2 antibody was 0.84, which was also better than these conventional methods. In conclusion, A novel methylation marker LBX2 could be used as a simple, cost-effective, and reliable diagnostic method for LNM of CRC.
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spelling doaj.art-78b1649cfc4a4ae6b5230a3221d986682022-12-22T02:35:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10008231000823A novel DNA methylation marker to identify lymph node metastasis of colorectal cancerYingdian Yu0Wenyuan Xue1Zefeng Liu2Shang Chen3Jun Wang4Quanzhou Peng5Linhao Xu6Xin Liu7Chunhui Cui8Jian-Bing Fan9Jian-Bing Fan10Jian-Bing Fan11Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Zhujiang Hosipital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaAnchorDx Medical Co., Ltd., International Bio-Island, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaAnchorDx Medical Co., Ltd., International Bio-Island, Guangzhou, ChinaAnchorDx Medical Co., Ltd., International Bio-Island, Guangzhou, ChinaDepartment of General Surgery, Zhujiang Hosipital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaAnchorDx Medical Co., Ltd., International Bio-Island, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaLymph node metastasis (LNM) of colorectal cancer (CRC) is an important factor for both prognosis and treatment. Given the deficiencies of conventional tests, we aim to discover novel DNA methylation markers to efficiently identify LNM status of CRC. In this study, genome-wide methylation sequencing was performed in a cohort (n=30) using fresh CRC tissue to discover differentially methylated markers. These markers were subsequently validated with fluorescence quantitative PCR in a cohort (n=221), and the optimal marker was compared to conventional diagnostic methods. Meanwhile, immunohistochemistry was used to verify the effectiveness of the antibody corresponding to this marker in a cohort (n=56). LBX2 achieved an AUC of 0.87, specificity of 87.3%, sensitivity of 75.7%, and accuracy of 81.9%, which outperformed conventional methods including imaging (CT, PET-CT) with an AUC of 0.52, CA199 with an AUC of 0.58, CEA with an AUC of 0.56. LBX2 was also superior to clinicopathological indicators including the depth of tumor invasion and lymphatic invasion with an AUC of 0.61and 0.63 respectively. Moreover, the AUC of LBX2 antibody was 0.84, which was also better than these conventional methods. In conclusion, A novel methylation marker LBX2 could be used as a simple, cost-effective, and reliable diagnostic method for LNM of CRC.https://www.frontiersin.org/articles/10.3389/fonc.2022.1000823/fullcolorectal cancerlymph node metastasisDNA methylation markerimmunohistochemistrydiagnostic method
spellingShingle Yingdian Yu
Wenyuan Xue
Zefeng Liu
Shang Chen
Jun Wang
Quanzhou Peng
Linhao Xu
Xin Liu
Chunhui Cui
Jian-Bing Fan
Jian-Bing Fan
Jian-Bing Fan
A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
Frontiers in Oncology
colorectal cancer
lymph node metastasis
DNA methylation marker
immunohistochemistry
diagnostic method
title A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
title_full A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
title_fullStr A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
title_full_unstemmed A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
title_short A novel DNA methylation marker to identify lymph node metastasis of colorectal cancer
title_sort novel dna methylation marker to identify lymph node metastasis of colorectal cancer
topic colorectal cancer
lymph node metastasis
DNA methylation marker
immunohistochemistry
diagnostic method
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1000823/full
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