Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas

Chih Chi Kuo, Ching Yu Lin, Yu Lueng Shih, Chung Bao Hsieh, Pei Yu Lin, Shuh Bing Guan, Ming Song Hsieh, Hung Cheng Lai, Chien Jen Chen, Ya Wen Lin

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

Background: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC. Methods: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC. Results: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90%-96.7%) and comparable specificity (93.1%-96.6%) to each individual gene (33.3%-76.7% and 55.2%-100.0%). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p
原文英語
頁(從 - 到)1235-1245
頁數11
期刊Clinical Chemistry and Laboratory Medicine
52
發行號8
DOIs
出版狀態已發佈 - 八月 1 2014
對外發佈Yes

指紋

Methylation
Homeobox Genes
Tumors
Hepatocellular Carcinoma
Genes
Tissue
Plasmas
Neoplasms
Biomarkers
Polymerase Chain Reaction
DNA Methylation
Oligonucleotide Array Sequence Analysis
Genome
DNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Medicine(all)

引用此文

Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas. / Kuo, Chih Chi; Lin, Ching Yu; Shih, Yu Lueng; Hsieh, Chung Bao; Lin, Pei Yu; Guan, Shuh Bing; Hsieh, Ming Song; Lai, Hung Cheng; Chen, Chien Jen; Lin, Ya Wen.

於: Clinical Chemistry and Laboratory Medicine, 卷 52, 編號 8, 01.08.2014, p. 1235-1245.

研究成果: 雜誌貢獻文章

Kuo, Chih Chi ; Lin, Ching Yu ; Shih, Yu Lueng ; Hsieh, Chung Bao ; Lin, Pei Yu ; Guan, Shuh Bing ; Hsieh, Ming Song ; Lai, Hung Cheng ; Chen, Chien Jen ; Lin, Ya Wen. / Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas. 於: Clinical Chemistry and Laboratory Medicine. 2014 ; 卷 52, 編號 8. 頁 1235-1245.
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title = "Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas",
abstract = "Background: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC. Methods: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC. Results: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7{\%}; 23/30) compared with controls (3.4{\%}; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90{\%}-96.7{\%}) and comparable specificity (93.1{\%}-96.6{\%}) to each individual gene (33.3{\%}-76.7{\%} and 55.2{\%}-100.0{\%}). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p",
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T1 - Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas

AU - Kuo, Chih Chi

AU - Lin, Ching Yu

AU - Shih, Yu Lueng

AU - Hsieh, Chung Bao

AU - Lin, Pei Yu

AU - Guan, Shuh Bing

AU - Hsieh, Ming Song

AU - Lai, Hung Cheng

AU - Chen, Chien Jen

AU - Lin, Ya Wen

PY - 2014/8/1

Y1 - 2014/8/1

N2 - Background: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC. Methods: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC. Results: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90%-96.7%) and comparable specificity (93.1%-96.6%) to each individual gene (33.3%-76.7% and 55.2%-100.0%). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p

AB - Background: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC. Methods: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC. Results: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90%-96.7%) and comparable specificity (93.1%-96.6%) to each individual gene (33.3%-76.7% and 55.2%-100.0%). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p

KW - DNA methylation

KW - HCC biomarker

KW - HOXA9

KW - methylation array

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SN - 1434-6621

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