TITLE: Novel MicroRNA Diagnostic for IBD-associated Colorectal Cancer
CASE NUMBER: C10775
UNMET NEED
Chronic idiopathic inflammatory bowel disease (IBD) predisposes to the development of colorectal carcinoma. Current preventive measures to diminish colorectal cancer mortality in IBD patients consist of periodic surveillance colonoscopies with random biopsies combined with total colectomy if dysplasia or neoplasia are found. However, challenges regarding management and early detection of IBD-associated neoplasia (IBDN) still remain. Precancerous dysplastic lesions still escape detection. Distinguishing between IBD-caused dysplasia or neoplasia and sporadic adenoma or carcinoma is essential, since one diagnosis warrants total colectomy while the other can be treated with local excision. Therefore, it is important to develop new diagnostic strategies to better screen IBD individuals for colon cancer.
TECHNICAL DESCRIPTION
JHU researchers have identified microRNA as diagnostic biomarkers that can be used to differentiate or distinguish IBDN from sporadic colorectal cancer (S-CRC), IBD-Dysplasia, IBD and/or normal. MiR microarrays and quantitative RT-PCR were used to detect and confirm dysregulated miRs. Receiver-operating characteristic curve analysis was applied to evaluate the potential utility of miR-31 and miR-224 as a neoplastic disease marker in IBD. In silico prediction analysis, Western blot, and luciferase activity measurement were employed for target identification for miR-31. For miR-224 target mRNA identification, mRNA microarrays were employed in combination with bioinformatic analyses, Western blotting, and luciferase activity measurements.
MAJOR RESULTS
JHU researchers identified several dysregulated miRs between chronically inflamed mucosae and dysplasia arising in IBD. MiR-31 expression increases in a stepwise fashion during progression from normal to IBD to IBDN and accurately discriminated IBDNs from normal or chronically inflamed tissues in IBD patients. They also identified factor inhibiting hypoxia inducible factor 1 (FIH1) as a direct target of miR-31. They identified 30 miRs that were differentially expressed between chronically inflamed mucosae and cancers arising in IBD. MiR-224 levels increased successively at each stage of IBD progression and accurately discriminated cancers from normal or chronically inflamed IBD tissues. Cell cycle experiments indicated that miR-224 regulates the G1/S checkpoint in cell cycle regulation with p21 identified as a specific direct mRNA target of miR-224.
DISEASE INDICATION
Cancer/ IBD
ASSOCIATED PUBLICATIONS
■ PMC4259288 ■ PMC3006011 ■
TECHNOLOGY CLASSIFICATION
Primary Category: Diagnostics
Primary Subcategory: Research Tools
ASSOCIATED REPORTS OF INVENTION (ROIs) AND INTELLECTUAL PROPERTY (IP) FILING NUMBERS
ROI #: C10775
TITLE: Methods and compositions useful for diagnosing inflammatory bowel disease-associated neoplasia
STATUS: US Patent Pending
PRIORITY DATE: 5/3/2012
IP FILING NUMBERS: US 20150133330 A1
