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Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer

Early and specific detection of cancer provides an opportunity for appropriate treatment. Although studies have suggested that QKI is a tumor suppressor gene, no studies have evaluated the diagnostic utility of QKI methylation in colorectal cancer (CRC). Here, we evaluated the methylation status of...

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Autores principales: Zhang, Lei, Li, Dapeng, Gao, Lijing, Fu, Jinming, Sun, Simin, Huang, Hao, Zhang, Ding, Jia, Chenyang, Zheng, Ting, Cui, Binbin, Liu, Yanlong, Zhao, Yashuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395658/
https://www.ncbi.nlm.nih.gov/pubmed/36017498
http://dx.doi.org/10.3389/fgene.2022.928150
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author Zhang, Lei
Li, Dapeng
Gao, Lijing
Fu, Jinming
Sun, Simin
Huang, Hao
Zhang, Ding
Jia, Chenyang
Zheng, Ting
Cui, Binbin
Liu, Yanlong
Zhao, Yashuang
author_facet Zhang, Lei
Li, Dapeng
Gao, Lijing
Fu, Jinming
Sun, Simin
Huang, Hao
Zhang, Ding
Jia, Chenyang
Zheng, Ting
Cui, Binbin
Liu, Yanlong
Zhao, Yashuang
author_sort Zhang, Lei
collection PubMed
description Early and specific detection of cancer provides an opportunity for appropriate treatment. Although studies have suggested that QKI is a tumor suppressor gene, no studies have evaluated the diagnostic utility of QKI methylation in colorectal cancer (CRC). Here, we evaluated the methylation status of QKI by integrating the methylation data of tissues and cell lines of multiple cancer types. The diagnostic performance of QKI was analyzed in the discovery dataset from the TCGA CRC 450K array (n = 440) and tested in the test sets (n = 845) from the GEO. The methylation level of QKI was further validated in our independent dataset (n = 388) using targeted bisulfite sequencing. All detected CpG sites in the QKI promoter showed CRC-specific hypermethylation in 31 types of tumor tissues. In the discovery dataset, six consecutive CpG sites achieved high diagnostic performances, with AUCs ranging from 0.821 to 0.930. In the test set, a region (chr6: 163,834,452–163,834,924) including four consecutive CpG sites had robust diagnostic ability in distinguishing CRC and adenoma from normal samples. In the validation dataset, similar robust results were observed in both early- and advanced-stage CRC patients. In addition, QKI exhibited hypermethylation in the cfDNA of patients with CRC (n = 14). Collectively, the QKI promoter is a CRC-specific methylation biomarker and holds great promise for improving the diagnosis using minimally invasive biopsy.
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spelling pubmed-93956582022-08-24 Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer Zhang, Lei Li, Dapeng Gao, Lijing Fu, Jinming Sun, Simin Huang, Hao Zhang, Ding Jia, Chenyang Zheng, Ting Cui, Binbin Liu, Yanlong Zhao, Yashuang Front Genet Genetics Early and specific detection of cancer provides an opportunity for appropriate treatment. Although studies have suggested that QKI is a tumor suppressor gene, no studies have evaluated the diagnostic utility of QKI methylation in colorectal cancer (CRC). Here, we evaluated the methylation status of QKI by integrating the methylation data of tissues and cell lines of multiple cancer types. The diagnostic performance of QKI was analyzed in the discovery dataset from the TCGA CRC 450K array (n = 440) and tested in the test sets (n = 845) from the GEO. The methylation level of QKI was further validated in our independent dataset (n = 388) using targeted bisulfite sequencing. All detected CpG sites in the QKI promoter showed CRC-specific hypermethylation in 31 types of tumor tissues. In the discovery dataset, six consecutive CpG sites achieved high diagnostic performances, with AUCs ranging from 0.821 to 0.930. In the test set, a region (chr6: 163,834,452–163,834,924) including four consecutive CpG sites had robust diagnostic ability in distinguishing CRC and adenoma from normal samples. In the validation dataset, similar robust results were observed in both early- and advanced-stage CRC patients. In addition, QKI exhibited hypermethylation in the cfDNA of patients with CRC (n = 14). Collectively, the QKI promoter is a CRC-specific methylation biomarker and holds great promise for improving the diagnosis using minimally invasive biopsy. Frontiers Media S.A. 2022-08-09 /pmc/articles/PMC9395658/ /pubmed/36017498 http://dx.doi.org/10.3389/fgene.2022.928150 Text en Copyright © 2022 Zhang, Li, Gao, Fu, Sun, Huang, Zhang, Jia, Zheng, Cui, Liu and Zhao. 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 Genetics
Zhang, Lei
Li, Dapeng
Gao, Lijing
Fu, Jinming
Sun, Simin
Huang, Hao
Zhang, Ding
Jia, Chenyang
Zheng, Ting
Cui, Binbin
Liu, Yanlong
Zhao, Yashuang
Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title_full Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title_fullStr Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title_full_unstemmed Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title_short Promoter Methylation of QKI as a Potential Specific Biomarker for Early Detection of Colorectal Cancer
title_sort promoter methylation of qki as a potential specific biomarker for early detection of colorectal cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395658/
https://www.ncbi.nlm.nih.gov/pubmed/36017498
http://dx.doi.org/10.3389/fgene.2022.928150
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