Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic marker of colorectal cancer

Ruo Kai Lin, Wan Yu Hung, Yu Fang Huang, Yu Jia Chang, Chien Hsing Lin, Wei Yu Chen, Shih Feng Chiu, Shih Ching Chang, Shih Feng Tsai

研究成果: 雜誌貢獻文章

摘要

Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs) contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC) screening marker, we investigated DNA methylation alterations in novel TSGs. Using HumanMethylation450 BeadChip arrays, CpG regions in BEND5 were the most highly methylated among all genomic regions in 26 colorectal tumors compared to paired non-neoplastic tissues from a Taiwan cohort. Therefore, BEND5 was selected for further analysis. Quantitative methylation-specific real-time PCR revealed that 86.7% (117/135) of CRC patients exhibited hypermethylated BEND5. Real-time reverse transcription PCR identified that BEND5 mRNA expression was downregulated in 68% (32/47) of the analyzed samples. BEND5 hypermethylation was associated with poor overall survival (OS) in Taiwan patients with early-stage CRC (P = 0.037). In a CRC tissue set from South Korea, OS was higher in patients with high BEND5 protein expression than in those with low BEND5 protein expression (P = 0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation was associated with poor OS in patients with early-stage CRC in The Cancer Genome Atlas (TCGA) data set (P = 0.003). Multivariate Cox proportional hazards regression analysis further supported that hypermethylation of BEND5 genes was significantly associated with OS in Taiwan and TCGA CRC patients (P = 0.023 and 0.033, respectively). Finally, the cell model assay with transient transfection of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell proliferation. In conclusion, epigenetic alteration in the candidate TSG BEND5 contributes to colorectal cancer development and is a prognostic marker of CRC.

原文英語
頁(從 - 到)113431-113443
頁數13
期刊Oncotarget
8
發行號69
DOIs
出版狀態已發佈 - 一月 1 2017

指紋

Colorectal Neoplasms
Cell Proliferation
Tumor Suppressor Genes
Taiwan
Survival
Atlases
Genome
Neoplasms
Republic of Korea
CpG Islands
DNA Methylation
Early Detection of Cancer
Epigenomics
Methylation
Reverse Transcription
Transfection
Real-Time Polymerase Chain Reaction
Carcinogenesis
Proteins
Down-Regulation

ASJC Scopus subject areas

  • Oncology

引用此文

Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic marker of colorectal cancer. / Lin, Ruo Kai; Hung, Wan Yu; Huang, Yu Fang; Chang, Yu Jia; Lin, Chien Hsing; Chen, Wei Yu; Chiu, Shih Feng; Chang, Shih Ching; Tsai, Shih Feng.

於: Oncotarget, 卷 8, 編號 69, 01.01.2017, p. 113431-113443.

研究成果: 雜誌貢獻文章

Lin, Ruo Kai ; Hung, Wan Yu ; Huang, Yu Fang ; Chang, Yu Jia ; Lin, Chien Hsing ; Chen, Wei Yu ; Chiu, Shih Feng ; Chang, Shih Ching ; Tsai, Shih Feng. / Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic marker of colorectal cancer. 於: Oncotarget. 2017 ; 卷 8, 編號 69. 頁 113431-113443.
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title = "Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic marker of colorectal cancer",
abstract = "Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs) contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC) screening marker, we investigated DNA methylation alterations in novel TSGs. Using HumanMethylation450 BeadChip arrays, CpG regions in BEND5 were the most highly methylated among all genomic regions in 26 colorectal tumors compared to paired non-neoplastic tissues from a Taiwan cohort. Therefore, BEND5 was selected for further analysis. Quantitative methylation-specific real-time PCR revealed that 86.7{\%} (117/135) of CRC patients exhibited hypermethylated BEND5. Real-time reverse transcription PCR identified that BEND5 mRNA expression was downregulated in 68{\%} (32/47) of the analyzed samples. BEND5 hypermethylation was associated with poor overall survival (OS) in Taiwan patients with early-stage CRC (P = 0.037). In a CRC tissue set from South Korea, OS was higher in patients with high BEND5 protein expression than in those with low BEND5 protein expression (P = 0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation was associated with poor OS in patients with early-stage CRC in The Cancer Genome Atlas (TCGA) data set (P = 0.003). Multivariate Cox proportional hazards regression analysis further supported that hypermethylation of BEND5 genes was significantly associated with OS in Taiwan and TCGA CRC patients (P = 0.023 and 0.033, respectively). Finally, the cell model assay with transient transfection of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell proliferation. In conclusion, epigenetic alteration in the candidate TSG BEND5 contributes to colorectal cancer development and is a prognostic marker of CRC.",
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author = "Lin, {Ruo Kai} and Hung, {Wan Yu} and Huang, {Yu Fang} and Chang, {Yu Jia} and Lin, {Chien Hsing} and Chen, {Wei Yu} and Chiu, {Shih Feng} and Chang, {Shih Ching} and Tsai, {Shih Feng}",
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T1 - Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic marker of colorectal cancer

AU - Lin, Ruo Kai

AU - Hung, Wan Yu

AU - Huang, Yu Fang

AU - Chang, Yu Jia

AU - Lin, Chien Hsing

AU - Chen, Wei Yu

AU - Chiu, Shih Feng

AU - Chang, Shih Ching

AU - Tsai, Shih Feng

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs) contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC) screening marker, we investigated DNA methylation alterations in novel TSGs. Using HumanMethylation450 BeadChip arrays, CpG regions in BEND5 were the most highly methylated among all genomic regions in 26 colorectal tumors compared to paired non-neoplastic tissues from a Taiwan cohort. Therefore, BEND5 was selected for further analysis. Quantitative methylation-specific real-time PCR revealed that 86.7% (117/135) of CRC patients exhibited hypermethylated BEND5. Real-time reverse transcription PCR identified that BEND5 mRNA expression was downregulated in 68% (32/47) of the analyzed samples. BEND5 hypermethylation was associated with poor overall survival (OS) in Taiwan patients with early-stage CRC (P = 0.037). In a CRC tissue set from South Korea, OS was higher in patients with high BEND5 protein expression than in those with low BEND5 protein expression (P = 0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation was associated with poor OS in patients with early-stage CRC in The Cancer Genome Atlas (TCGA) data set (P = 0.003). Multivariate Cox proportional hazards regression analysis further supported that hypermethylation of BEND5 genes was significantly associated with OS in Taiwan and TCGA CRC patients (P = 0.023 and 0.033, respectively). Finally, the cell model assay with transient transfection of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell proliferation. In conclusion, epigenetic alteration in the candidate TSG BEND5 contributes to colorectal cancer development and is a prognostic marker of CRC.

AB - Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs) contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC) screening marker, we investigated DNA methylation alterations in novel TSGs. Using HumanMethylation450 BeadChip arrays, CpG regions in BEND5 were the most highly methylated among all genomic regions in 26 colorectal tumors compared to paired non-neoplastic tissues from a Taiwan cohort. Therefore, BEND5 was selected for further analysis. Quantitative methylation-specific real-time PCR revealed that 86.7% (117/135) of CRC patients exhibited hypermethylated BEND5. Real-time reverse transcription PCR identified that BEND5 mRNA expression was downregulated in 68% (32/47) of the analyzed samples. BEND5 hypermethylation was associated with poor overall survival (OS) in Taiwan patients with early-stage CRC (P = 0.037). In a CRC tissue set from South Korea, OS was higher in patients with high BEND5 protein expression than in those with low BEND5 protein expression (P = 0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation was associated with poor OS in patients with early-stage CRC in The Cancer Genome Atlas (TCGA) data set (P = 0.003). Multivariate Cox proportional hazards regression analysis further supported that hypermethylation of BEND5 genes was significantly associated with OS in Taiwan and TCGA CRC patients (P = 0.023 and 0.033, respectively). Finally, the cell model assay with transient transfection of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell proliferation. In conclusion, epigenetic alteration in the candidate TSG BEND5 contributes to colorectal cancer development and is a prognostic marker of CRC.

KW - BEND5

KW - Colorectal cancer

KW - DNA methylation

KW - Prognostic marker

KW - Tumor suppressor genes

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