Methylated eyes absent 4 (EγA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer: Evidence for a field effect

John B Kisiel, Megan M. Garrity-Park, William R. Taylor, Thomas Christopher Smyrk, David A. Ahlquist

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both tissue and stool. It is not known if mEYA4 is also present in nonadjacent non-neoplastic mucosa (NNM) of UC patients with colorectal neoplasia. Methods: Formalin-fixed tissues from 25 UC cases with colorectal cancer (CRC) and 25 UC controls with neither CRC nor dysplasia were matched on gender, age, disease duration, disease extent, and coexistence of primary sclerosing cholangitis. DNA was extracted from sections of CRC and NNM from cases and UC control mucosae. Bisulfite-treated DNA was amplified using real-time methylation-specific PCR. The Wilcoxon rank-sum test assessed differences in mEYA4 levels from CRC, NNM, and control samples. Logistic regression was used to estimate sensitivity and specificity. Results: Sufficient DNA was available for 20 cases and 20 controls. The median mEYA4 level (with interquartile range) was 2 (0-5.7) in control mucosae but 93 (38.5-306) in CRC (P < 0.0001) and 27.4 (3-140) in NNM (P = 0.0009). At 95% specificity, mEYA4 was present in 80% of CRC and 50% of NNM tissue samples. The odds ratio of mEYA4 in NNM as an indicator of synchronous CRC was 19 (95% confidence interval, 2-170). Conclusions: The authors demonstrate significantly higher mEYA4 levels in NNM and synchronous CRC from UC cases than in colorectal mucosae of UC controls without neoplasia. The finding of this CRC-associated field change has important implications to the use of mEYA4 as a potential UC surveillance marker in tissue or stool.

Original languageEnglish (US)
Pages (from-to)2079-2083
Number of pages5
JournalInflammatory Bowel Diseases
Volume19
Issue number10
DOIs
StatePublished - Sep 2013

Fingerprint

Ulcerative Colitis
Colorectal Neoplasms
Methylation
Mucous Membrane
Genes
Nonparametric Statistics
DNA
Neoplasms
Sclerosing Cholangitis
Formaldehyde
Logistic Models
Odds Ratio
Confidence Intervals
Sensitivity and Specificity
Polymerase Chain Reaction

Keywords

  • Biological markers
  • DNA methylation
  • Field cancerization defect
  • Inflammatory bowel disease/complications
  • Neoplasms/genetics

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Methylated eyes absent 4 (EγA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer : Evidence for a field effect. / Kisiel, John B; Garrity-Park, Megan M.; Taylor, William R.; Smyrk, Thomas Christopher; Ahlquist, David A.

In: Inflammatory Bowel Diseases, Vol. 19, No. 10, 09.2013, p. 2079-2083.

Research output: Contribution to journalArticle

Kisiel, John B ; Garrity-Park, Megan M. ; Taylor, William R. ; Smyrk, Thomas Christopher ; Ahlquist, David A. / Methylated eyes absent 4 (EγA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer : Evidence for a field effect. In: Inflammatory Bowel Diseases. 2013 ; Vol. 19, No. 10. pp. 2079-2083.
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abstract = "Background: Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both tissue and stool. It is not known if mEYA4 is also present in nonadjacent non-neoplastic mucosa (NNM) of UC patients with colorectal neoplasia. Methods: Formalin-fixed tissues from 25 UC cases with colorectal cancer (CRC) and 25 UC controls with neither CRC nor dysplasia were matched on gender, age, disease duration, disease extent, and coexistence of primary sclerosing cholangitis. DNA was extracted from sections of CRC and NNM from cases and UC control mucosae. Bisulfite-treated DNA was amplified using real-time methylation-specific PCR. The Wilcoxon rank-sum test assessed differences in mEYA4 levels from CRC, NNM, and control samples. Logistic regression was used to estimate sensitivity and specificity. Results: Sufficient DNA was available for 20 cases and 20 controls. The median mEYA4 level (with interquartile range) was 2 (0-5.7) in control mucosae but 93 (38.5-306) in CRC (P < 0.0001) and 27.4 (3-140) in NNM (P = 0.0009). At 95{\%} specificity, mEYA4 was present in 80{\%} of CRC and 50{\%} of NNM tissue samples. The odds ratio of mEYA4 in NNM as an indicator of synchronous CRC was 19 (95{\%} confidence interval, 2-170). Conclusions: The authors demonstrate significantly higher mEYA4 levels in NNM and synchronous CRC from UC cases than in colorectal mucosae of UC controls without neoplasia. The finding of this CRC-associated field change has important implications to the use of mEYA4 as a potential UC surveillance marker in tissue or stool.",
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T1 - Methylated eyes absent 4 (EγA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer

T2 - Evidence for a field effect

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AU - Garrity-Park, Megan M.

AU - Taylor, William R.

AU - Smyrk, Thomas Christopher

AU - Ahlquist, David A.

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N2 - Background: Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both tissue and stool. It is not known if mEYA4 is also present in nonadjacent non-neoplastic mucosa (NNM) of UC patients with colorectal neoplasia. Methods: Formalin-fixed tissues from 25 UC cases with colorectal cancer (CRC) and 25 UC controls with neither CRC nor dysplasia were matched on gender, age, disease duration, disease extent, and coexistence of primary sclerosing cholangitis. DNA was extracted from sections of CRC and NNM from cases and UC control mucosae. Bisulfite-treated DNA was amplified using real-time methylation-specific PCR. The Wilcoxon rank-sum test assessed differences in mEYA4 levels from CRC, NNM, and control samples. Logistic regression was used to estimate sensitivity and specificity. Results: Sufficient DNA was available for 20 cases and 20 controls. The median mEYA4 level (with interquartile range) was 2 (0-5.7) in control mucosae but 93 (38.5-306) in CRC (P < 0.0001) and 27.4 (3-140) in NNM (P = 0.0009). At 95% specificity, mEYA4 was present in 80% of CRC and 50% of NNM tissue samples. The odds ratio of mEYA4 in NNM as an indicator of synchronous CRC was 19 (95% confidence interval, 2-170). Conclusions: The authors demonstrate significantly higher mEYA4 levels in NNM and synchronous CRC from UC cases than in colorectal mucosae of UC controls without neoplasia. The finding of this CRC-associated field change has important implications to the use of mEYA4 as a potential UC surveillance marker in tissue or stool.

AB - Background: Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both tissue and stool. It is not known if mEYA4 is also present in nonadjacent non-neoplastic mucosa (NNM) of UC patients with colorectal neoplasia. Methods: Formalin-fixed tissues from 25 UC cases with colorectal cancer (CRC) and 25 UC controls with neither CRC nor dysplasia were matched on gender, age, disease duration, disease extent, and coexistence of primary sclerosing cholangitis. DNA was extracted from sections of CRC and NNM from cases and UC control mucosae. Bisulfite-treated DNA was amplified using real-time methylation-specific PCR. The Wilcoxon rank-sum test assessed differences in mEYA4 levels from CRC, NNM, and control samples. Logistic regression was used to estimate sensitivity and specificity. Results: Sufficient DNA was available for 20 cases and 20 controls. The median mEYA4 level (with interquartile range) was 2 (0-5.7) in control mucosae but 93 (38.5-306) in CRC (P < 0.0001) and 27.4 (3-140) in NNM (P = 0.0009). At 95% specificity, mEYA4 was present in 80% of CRC and 50% of NNM tissue samples. The odds ratio of mEYA4 in NNM as an indicator of synchronous CRC was 19 (95% confidence interval, 2-170). Conclusions: The authors demonstrate significantly higher mEYA4 levels in NNM and synchronous CRC from UC cases than in colorectal mucosae of UC controls without neoplasia. The finding of this CRC-associated field change has important implications to the use of mEYA4 as a potential UC surveillance marker in tissue or stool.

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KW - Neoplasms/genetics

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