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DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma

BACKGROUND: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 (PAX1) and sex-determining region Y-related high-...

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Autores principales: Huang, Jin, Tan, Zhi-Rong, Yu, Jing, Li, He, Lv, Qiao-Li, Shao, Ying-Ying, Zhou, Hong-Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628670/
https://www.ncbi.nlm.nih.gov/pubmed/29033587
http://dx.doi.org/10.2147/OTT.S143389
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author Huang, Jin
Tan, Zhi-Rong
Yu, Jing
Li, He
Lv, Qiao-Li
Shao, Ying-Ying
Zhou, Hong-Hao
author_facet Huang, Jin
Tan, Zhi-Rong
Yu, Jing
Li, He
Lv, Qiao-Li
Shao, Ying-Ying
Zhou, Hong-Hao
author_sort Huang, Jin
collection PubMed
description BACKGROUND: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 (PAX1) and sex-determining region Y-related high-mobility group box 1 (SOX1) genes in CRC tissues. METHODS: DNA methylation at cg2,09,07,471 PAX1 and cg0,66,75,478 SOX1 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of PAX1 and SOX1 were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively. RESULTS: Methylation levels of PAX1/SOX1 genes were significantly higher in cancer tissues than in paired normal tissues. PAX1 and SOX1 genes were methylated in 28 (68.3%) of the 41 CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both P<0.001), respectively. Sensitivities and specificities of PAX1 methylation for the detection of cancer were 68.3% and 87.8%, respectively, whereas the corresponding values for SOX1 were 68.3% and 100%. However, the Kaplan–Meier analysis illustrated no significant difference in the overall survivals between patients with high and low methylation levels of SOX1 or PAX1 (P>0.5). In addition, the methylation level of PAX1/SOX1 was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stage I/II, 1.26±2.94, P<0.05). Relative RNA and protein expression levels of PAX1/SOX1 were both significantly lower in CRC tissues than in their paired normal tissue. CONCLUSIONS: This study is the first analysis of the methylation of PAX1/SOX1, which may be new biomarkers for CRC screening.
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spelling pubmed-56286702017-10-13 DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma Huang, Jin Tan, Zhi-Rong Yu, Jing Li, He Lv, Qiao-Li Shao, Ying-Ying Zhou, Hong-Hao Onco Targets Ther Clinical Trial Report BACKGROUND: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 (PAX1) and sex-determining region Y-related high-mobility group box 1 (SOX1) genes in CRC tissues. METHODS: DNA methylation at cg2,09,07,471 PAX1 and cg0,66,75,478 SOX1 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of PAX1 and SOX1 were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively. RESULTS: Methylation levels of PAX1/SOX1 genes were significantly higher in cancer tissues than in paired normal tissues. PAX1 and SOX1 genes were methylated in 28 (68.3%) of the 41 CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both P<0.001), respectively. Sensitivities and specificities of PAX1 methylation for the detection of cancer were 68.3% and 87.8%, respectively, whereas the corresponding values for SOX1 were 68.3% and 100%. However, the Kaplan–Meier analysis illustrated no significant difference in the overall survivals between patients with high and low methylation levels of SOX1 or PAX1 (P>0.5). In addition, the methylation level of PAX1/SOX1 was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stage I/II, 1.26±2.94, P<0.05). Relative RNA and protein expression levels of PAX1/SOX1 were both significantly lower in CRC tissues than in their paired normal tissue. CONCLUSIONS: This study is the first analysis of the methylation of PAX1/SOX1, which may be new biomarkers for CRC screening. Dove Medical Press 2017-09-26 /pmc/articles/PMC5628670/ /pubmed/29033587 http://dx.doi.org/10.2147/OTT.S143389 Text en © 2017 Huang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Clinical Trial Report
Huang, Jin
Tan, Zhi-Rong
Yu, Jing
Li, He
Lv, Qiao-Li
Shao, Ying-Ying
Zhou, Hong-Hao
DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title_full DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title_fullStr DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title_full_unstemmed DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title_short DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma
title_sort dna hypermethylated status and gene expression of pax1/sox1 in patients with colorectal carcinoma
topic Clinical Trial Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628670/
https://www.ncbi.nlm.nih.gov/pubmed/29033587
http://dx.doi.org/10.2147/OTT.S143389
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