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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)1235-1245
Number of pages11
JournalClinical Chemistry and Laboratory Medicine
Volume52
Issue number8
DOIs
Publication statusPublished - Aug 1 2014
Externally publishedYes

Fingerprint

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

Keywords

  • DNA methylation
  • HCC biomarker
  • HOXA9
  • methylation array

ASJC Scopus subject areas

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

Cite this

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.

In: Clinical Chemistry and Laboratory Medicine, Vol. 52, No. 8, 01.08.2014, p. 1235-1245.

Research output: Contribution to journalArticle

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. In: Clinical Chemistry and Laboratory Medicine. 2014 ; Vol. 52, No. 8. pp. 1235-1245.
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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

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KW - HCC biomarker

KW - HOXA9

KW - methylation array

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