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Plasma MicroRNA mirrors Tissue MicroRNA and Distinguishes Colorectal Cancer
Susan Galandiuk, Ziad Kanaan*, Maurice Robert Eichenberger*, Henry Roberts*, Bobby Keskey*, Xiaobin Yuan*, Shesh Rai*
University of Louisville, Louisville, KY

OBJECTIVE(S): Colorectal cancer(CRC), a leading cause of death, is curable if detected early. There is an unmet need for an accurate, non-invasive CRC biomarker. MicroRNAs(miRNAs) are non-protein-coding RNAs regulating gene expression that play a role in CRC development.
METHODS: MicroRNAs were evaluated in 3 patient groups. Levels of 384 miRNAs were determined using micro-fluidic array technology(Applied BioSystems®) in a training cohort of 30 CRC patients from whom cancer and adjacent normal tissue were collected. The four most dysregulated miRNAs (p<0.05,False Discovery Rate:10%) were then validated in a second blinded test cohort of 16 CRC patients. Validated tissue microRNAs were then evaluated in the plasma of a third group consisting of 20 CRC patients and 20 age-, gender-, and race-matched controls.
RESULTS: 19 of 384 miRNAs were dysregulated in CRC tissue in the training cohort (p<0.05, FDR: 10%). The two most upregulated(miR-31;miR-135b) and most downregulated (miR-1;miR-133a) miRNAs identified CRC in our test cohort with 100% sensitivity and 80% specificity. miR-31 was more upregulated in Stages III&IV compared to Stages I&II(p<0.05). In plasma of the third group, miR-21, the next most up-regulated tissue miRNA, differentiated CRC patients from controls with 90% specificity and sensitivity(table).
CONCLUSION: Plasma microRNAs provide reliable, non-invasive and inexpensive marker for CRC. This microRNA panel warrants study in larger cohorts. It appears uniquely promising as a plasma test for CRC.
MicroRNA-21 fold changes in plasma of CRC patients as compared to 20 age-, gender-, and race-matched controls
Matched PairFold ChangeMatched PairFold ChangeMatched PairFold ChangeMatched PairFold Change
15.4 6306.9 114.1 163.5
217.6 70.5* 123.0 1712.3
345.6 8279.2 1332.9 181.9
41872.6 99.5 14362.5 1927.2
51274.2 100.12* 1548.6 20324.1
*Fold change >1 denotes upregulation of miR-21. Matched pairs 7 and 10 showed downregulation of miR-21.

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