P-158 Differences in Gene Expression in UC Patients Harboring Remote Neoplasia Compared to UC Patients without Dysplasia

Colonoscopy, the current standard of care to detect neoplasia in patients with long-standing ulcerative colitis (UC), is invasive, costly, and can easily miss flat lesions. In previous studies, we demonstrated that UC patients who harbor a remote neoplastic lesion can be distinguished from normal controls and UC patients without neoplasia by differences in gene expression in normal appearing non-dysplastic rectal mucosa. In a larger cohort of subjects, we sought to validate changes in these genes from the rectal mucosa as clinical biomarkers distinguishing UC patients with neoplasia from UC patients without neoplasia. Forty-two RNA samples (UC without neoplasia: n = 22 subjects; UC harboring remote neoplasia: n = 20 subjects) were analyzed using the Illumina HumanHT-12 v4 BeadChip. Quality check and data normalization were done using the R/Biocondutor package lumi implementing an RMA approach. To identify differentially expressed genes, a 2-group comparison was performed using Significance Analysis of Microarrays (SAM) software with a false discovery rate (FDR) <5%. Functional enrichment analysis of the identified differentially expressed genes or SOM clusters was performed using Onto-Express and Ingenuity software. We identified 329 significantly up-regulated genes and 264 significantly down-regulated genes in UC patients harboring remote neoplasia compared to UC patients without neoplasia (fold change >2, P < 0.001). Functionally enriched networks included pathways of complement activation, IL-17 signaling, angiogenesis, as well as NFκβ and FOS regulated pathways. Many genes, which we found were dysregulated in a previous analysis of UC patients harboring remote neoplasia, were confirmed in this independent and larger cohort, including Reg1a, Reg3a, S100A8, S100A9, AQP8, and CLDN8. In a large independent cohort, we confirmed that UC patients harboring a remote neoplastic lesion demonstrate significant differences in gene expression in rectal mucosa compared to UC patients without neoplasia. These results validate many of the differentially expressed genes identified in our prior studies. These findings, moreover, provide additional insights into mechanisms driving UC-associated neoplastic transformation that could lead to the development of less invasive and more accurate methods of detection in this high-risk population.