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A Plasma MicroRNA Panel for Detection of Advanced Colorectal Adenomas
Susan Galandiuk, Ziad Kanaan*, M.Robert Eichenberger*, Henry Roberts*, Clayton Weller*, Jianmin Pan*, Shesh Rai*
University of Louisville, Louisville, KY

OBJECTIVE(S): Detection of pre-cancerous lesions (advanced adenomas >10mm) is key to reducing colorectal cancer (CRC) mortality. There is need for accurate, non-invasive biomarkers for detection of such lesions. MicroRNAs (miRNAs) are non-protein-coding RNAs that regulate gene expression. In follow-up to our prior work investigating dysregulation of 5 plasma miRNAs in CRC patients, we undertook a more comprehensive plasma-miRNA screening study in patients with advanced adenomas and patients with CRC.
METHODS: Plasma screening of 384 miRNAs was determined using micro-fluidic array technology (Applied BioSystems®) in a training cohort of 10 healthy controls, 9 patients with advanced adenomas, and 10 patients with CRC. A panel of the most dysregulated miRNAs (p<0.05,False Discovery Rate:5%) were then validated in a blinded test cohort of 10 different healthy controls, 9 patients with advanced adenomas, and 10 patients with CRC.
RESULTS: A panel of 4 plasma miRNAs (miR-17, miR-195, miR-331, and miR-142-3p) distinguished polyps from controls with >90% sensitivity and specificity. Additionally, a panel of 6 plasma miRNAs (miR-431, miR-15b, miR-139-3p, miR-142-3p, miR-331, miR-21) distinguished CRC from controls with >90% sensitivity and specificity. Receiver-operating-characteristic (ROC) curves were demonstrated and area-under-the-curve (AUC) values were calculated (figure)
CONCLUSIONS: Plasma microRNAs provide reliable, non-invasive and inexpensive marker for advanced adenomas. This microRNA panel warrants study in larger cohorts. Such a plasma-based assay could provide better screening compliance as compared to stool-based or endoscopic screening.


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