title: A Biomarker Panel to Detect Synchronous Neoplasm in Non-neoplastic Surveillance Biopsies from Patients with Ulcerative Colitis.
abstract: 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.
  
  
  
  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-α, IL-1β, 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.
  
  
  
  Comparison of nonadjacent, non-dysplastic DNA from UC-neoplasm patients versus UC-controls indicated that TNF-α, IL-1β, 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.
  
  
  
  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.
authors.affiliation: Divisions of *Experimental Pathology and Medicine, †Gastroenterology and Hepatology, ‡Biostatistics, and §Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Garrity-Park
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Bryant
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000473:pathology*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D018123:Receptors, Interleukin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; C515500:IL23R protein, human; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D018123:Receptors, Interleukin; C493729:Runx3 protein, human; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human