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Author (up) Garrity-Park, M.M.; Loftus, E.V.J.; Bryant, S.C.; Smyrk, T.C. url  doi
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  Title A Biomarker Panel to Detect Synchronous Neoplasm in Non-neoplastic Surveillance Biopsies from Patients with Ulcerative Colitis Type Journal Article
  Year 2016 Publication Inflammatory Bowel Diseases Abbreviated Journal Inflamm Bowel Dis  
  Volume 22 Issue 7 Pages 1568-1574  
  Keywords  
  Abstract BACKGROUND: Patients with ulcerative colitis (UC) are at risk for colorectal neoplasia. Challenges associated with surveillance colonoscopy with random biopsies for detection of dysplasia/cancer are well-documented. This study extended our findings in UC-associated colorectal cancer to include low-grade dysplasia (LGD) patients, testing whether our biomarker panel detects any UC-associated neoplasm. METHODS: DNA from the LGD area and the corresponding nonadjacent, non-dysplastic section from 171 UC-LGD patients was extracted. TaqMan SNP Genotyping Assays for TNF-alpha, IL-1beta, and IL23R were used to evaluate polymorphisms for each gene. Bisulfite-treated DNA was used for methylation testing of RUNX3, COX2, and MINT1. LGD data were combined with UC-cancer patient data for statistical testing. Logistic regression analyses determined associations between genetic/epigenetic/clinical variables and UC-associated neoplasia. Receiver operating characteristic analyses were performed to determine the final synchronous neoplasm detection panel. RESULTS: Comparison of nonadjacent, non-dysplastic DNA from UC-neoplasm patients versus UC-controls indicated that TNF-alpha, IL-1beta, and methylation of RUNX3, MINT1, and COX2 were significantly different (P < 0.0001). In multivariable analysis, all remained significant with an area under the curve of 0.85, exceeding the clinical variable panel area under the curve. Combining clinical and experimental variables yielded a neoplasm biomarker panel with an area under the curve of 0.95 (sensitivity and specificity of 82% and 91%, respectively). Analysis of DNA from LGD with known progression compared with LGD without progression indicated a significant difference in RUNX3 methylation. CONCLUSIONS: A combined clinical, genetic, and epigenetic model for detecting synchronous neoplasm by testing of non-neoplastic colonic tissue had favorable operating characteristics and could complement current patient care.  
  Address Divisions of *Experimental Pathology and Medicine, daggerGastroenterology and Hepatology, double daggerBiostatistics, and section signAnatomic Pathology, Mayo Clinic, Rochester, Minnesota  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1078-0998 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27135485 Approved no  
  Call Number ref @ user @ Serial 96380  
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