Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma

Pyrosequencing is considered the gold standard for methylation detection. Using pyrosequencing to detect the DNA methylation statue of PAX1, SOX1 and ZNF582 in ESCC. The receiver operating characteristic curves showed that the detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2019-12, Vol.120, p.109488-109488, Article 109488
Hauptverfasser: Tang, Li, Liou, Yu-Ligh, Wan, Zi-Rui, Tang, Jie, Zhou, Yuan, Zhuang, Wei, Wang, Guo
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container_title Biomedicine & pharmacotherapy
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Liou, Yu-Ligh
Wan, Zi-Rui
Tang, Jie
Zhou, Yuan
Zhuang, Wei
Wang, Guo
description Pyrosequencing is considered the gold standard for methylation detection. Using pyrosequencing to detect the DNA methylation statue of PAX1, SOX1 and ZNF582 in ESCC. The receiver operating characteristic curves showed that the detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis. [Display omitted] •Gene methylation is one of the importance causes of cancer.•The methylation levels of PAX1, SOX1, and ZNF582 genes were significantly higher in ESCC tissues than non-cancerous tissues.•Hypermethylation of PAX1, SOX1 and ZNF582 was an independent risk factor of ESCC development.•Detection of PAX1/SOX1/ZNF582 methylation status has excellent sensitivity and specificity of ESCC diagnosis. Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival. Pyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC. The methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P 
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Using pyrosequencing to detect the DNA methylation statue of PAX1, SOX1 and ZNF582 in ESCC. The receiver operating characteristic curves showed that the detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis. [Display omitted] •Gene methylation is one of the importance causes of cancer.•The methylation levels of PAX1, SOX1, and ZNF582 genes were significantly higher in ESCC tissues than non-cancerous tissues.•Hypermethylation of PAX1, SOX1 and ZNF582 was an independent risk factor of ESCC development.•Detection of PAX1/SOX1/ZNF582 methylation status has excellent sensitivity and specificity of ESCC diagnosis. Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival. Pyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC. The methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P &lt; 0.0001). The accuracy, sensitivity and specificity of PAX1 methylation for the detection of cancer were respectively 0.754, 96.0% and 51.4%; for SOX1 which were 0.781, 89.2% and 59.5%; for ZNF582 which were 0.898, 93.2% and 75.7%. Most importantly, both the sensitivity and specificity of ZNF582 methylation testing achieved 100% in female ESCC patients. Hypermethylation of PAX1/SOX1/ZNF582 exhibited as an independent risk factor for ESCC development. In addition, ZNF582 methylation level in tumor tissue from the female patients was higher than that from male patients, and it was higher in the moderate and poor differentiated tumors compared to that in well-differentiated tumors. SOX1 methylation level was significantly higher in tumors located in the upper region than those located in the middle or lower regions. The methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues than in paired-adjacent and normal tissues, suggesting that detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis.</description><identifier>ISSN: 0753-3322</identifier><identifier>EISSN: 1950-6007</identifier><identifier>DOI: 10.1016/j.biopha.2019.109488</identifier><identifier>PMID: 31629253</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Biomarkers, Tumor - genetics ; Cell Differentiation - genetics ; DNA methylation ; DNA Methylation - genetics ; Esophageal Neoplasms - genetics ; Esophageal squamous cell carcinoma ; Esophageal Squamous Cell Carcinoma - genetics ; Female ; Humans ; Kruppel-Like Transcription Factors - genetics ; Male ; Middle Aged ; Paired Box Transcription Factors - genetics ; PAX1 ; SOX1 ; SOXB1 Transcription Factors - genetics ; ZNF582</subject><ispartof>Biomedicine &amp; pharmacotherapy, 2019-12, Vol.120, p.109488-109488, Article 109488</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-74a66e1b3ea6b6b8d903a471167bc766320da2a7c1a938b1447162d820f120773</citedby><cites>FETCH-LOGICAL-c408t-74a66e1b3ea6b6b8d903a471167bc766320da2a7c1a938b1447162d820f120773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopha.2019.109488$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31629253$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Li</creatorcontrib><creatorcontrib>Liou, Yu-Ligh</creatorcontrib><creatorcontrib>Wan, Zi-Rui</creatorcontrib><creatorcontrib>Tang, Jie</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Zhuang, Wei</creatorcontrib><creatorcontrib>Wang, Guo</creatorcontrib><title>Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma</title><title>Biomedicine &amp; pharmacotherapy</title><addtitle>Biomed Pharmacother</addtitle><description>Pyrosequencing is considered the gold standard for methylation detection. Using pyrosequencing to detect the DNA methylation statue of PAX1, SOX1 and ZNF582 in ESCC. The receiver operating characteristic curves showed that the detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis. [Display omitted] •Gene methylation is one of the importance causes of cancer.•The methylation levels of PAX1, SOX1, and ZNF582 genes were significantly higher in ESCC tissues than non-cancerous tissues.•Hypermethylation of PAX1, SOX1 and ZNF582 was an independent risk factor of ESCC development.•Detection of PAX1/SOX1/ZNF582 methylation status has excellent sensitivity and specificity of ESCC diagnosis. Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival. Pyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC. The methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P &lt; 0.0001). The accuracy, sensitivity and specificity of PAX1 methylation for the detection of cancer were respectively 0.754, 96.0% and 51.4%; for SOX1 which were 0.781, 89.2% and 59.5%; for ZNF582 which were 0.898, 93.2% and 75.7%. Most importantly, both the sensitivity and specificity of ZNF582 methylation testing achieved 100% in female ESCC patients. Hypermethylation of PAX1/SOX1/ZNF582 exhibited as an independent risk factor for ESCC development. In addition, ZNF582 methylation level in tumor tissue from the female patients was higher than that from male patients, and it was higher in the moderate and poor differentiated tumors compared to that in well-differentiated tumors. SOX1 methylation level was significantly higher in tumors located in the upper region than those located in the middle or lower regions. The methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues than in paired-adjacent and normal tissues, suggesting that detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal squamous cell carcinoma</subject><subject>Esophageal Squamous Cell Carcinoma - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Paired Box Transcription Factors - genetics</subject><subject>PAX1</subject><subject>SOX1</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>ZNF582</subject><issn>0753-3322</issn><issn>1950-6007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhq0K1C6lb1AhHzmQZWwndnJBWhUKSFWLBEgVF2viTFovSby1s5X69niVwpGTpZlvPP98jJ0LWAsQ-v123fqwu8e1BNHkUlPW9RFbiaaCQgOYF2wFplKFUlKesFcpbQGg0qo-ZidKaNnISq3Y46alGHGa-cfrDR9pvn8acPZh4qHn3za34h3_fnMrOE4d_3V9WdWS39FEiWPiuzDTNHsceE4yYvxNMfE-RE7pEOyOcic97HEM-8QdDQN3GJ2fMvuavexxSHT2_J6yn5efflx8Ka5uPn-92FwVroR6LkyJWpNoFaFudVt3DSgsjRDatM5orSR0KNE4gY2qW1HmnpZdLaEXEoxRp-zt8u8uhoc9pdmOPh2i4EQ5lZUKjCgrWVYZLRfUxZBSpN7uos9XPVkB9mDcbu1i3B6M28V4HnvzvGHfjtT9G_qrOAMfFoDynY-eok3O0-So85HcbLvg_7_hD1L1kc4</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>Tang, Li</creator><creator>Liou, Yu-Ligh</creator><creator>Wan, Zi-Rui</creator><creator>Tang, Jie</creator><creator>Zhou, Yuan</creator><creator>Zhuang, Wei</creator><creator>Wang, Guo</creator><general>Elsevier Masson SAS</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201912</creationdate><title>Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma</title><author>Tang, Li ; Liou, Yu-Ligh ; Wan, Zi-Rui ; Tang, Jie ; Zhou, Yuan ; Zhuang, Wei ; Wang, Guo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-74a66e1b3ea6b6b8d903a471167bc766320da2a7c1a938b1447162d820f120773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal squamous cell carcinoma</topic><topic>Esophageal Squamous Cell Carcinoma - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Paired Box Transcription Factors - genetics</topic><topic>PAX1</topic><topic>SOX1</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>ZNF582</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Li</creatorcontrib><creatorcontrib>Liou, Yu-Ligh</creatorcontrib><creatorcontrib>Wan, Zi-Rui</creatorcontrib><creatorcontrib>Tang, Jie</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Zhuang, Wei</creatorcontrib><creatorcontrib>Wang, Guo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biomedicine &amp; 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Using pyrosequencing to detect the DNA methylation statue of PAX1, SOX1 and ZNF582 in ESCC. The receiver operating characteristic curves showed that the detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis. [Display omitted] •Gene methylation is one of the importance causes of cancer.•The methylation levels of PAX1, SOX1, and ZNF582 genes were significantly higher in ESCC tissues than non-cancerous tissues.•Hypermethylation of PAX1, SOX1 and ZNF582 was an independent risk factor of ESCC development.•Detection of PAX1/SOX1/ZNF582 methylation status has excellent sensitivity and specificity of ESCC diagnosis. Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival. Pyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC. The methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P &lt; 0.0001). The accuracy, sensitivity and specificity of PAX1 methylation for the detection of cancer were respectively 0.754, 96.0% and 51.4%; for SOX1 which were 0.781, 89.2% and 59.5%; for ZNF582 which were 0.898, 93.2% and 75.7%. Most importantly, both the sensitivity and specificity of ZNF582 methylation testing achieved 100% in female ESCC patients. Hypermethylation of PAX1/SOX1/ZNF582 exhibited as an independent risk factor for ESCC development. In addition, ZNF582 methylation level in tumor tissue from the female patients was higher than that from male patients, and it was higher in the moderate and poor differentiated tumors compared to that in well-differentiated tumors. SOX1 methylation level was significantly higher in tumors located in the upper region than those located in the middle or lower regions. The methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues than in paired-adjacent and normal tissues, suggesting that detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>31629253</pmid><doi>10.1016/j.biopha.2019.109488</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Biomarkers, Tumor - genetics
Cell Differentiation - genetics
DNA methylation
DNA Methylation - genetics
Esophageal Neoplasms - genetics
Esophageal squamous cell carcinoma
Esophageal Squamous Cell Carcinoma - genetics
Female
Humans
Kruppel-Like Transcription Factors - genetics
Male
Middle Aged
Paired Box Transcription Factors - genetics
PAX1
SOX1
SOXB1 Transcription Factors - genetics
ZNF582
title Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma
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