Use of MicroRNAs to Screen for Colon Cancer

Abstract

Colon cancer (CC) screening is important for diagnosing early stage for malignancy and therefore potentially reduces mortality from this disease because the cancer could be cured at the early disease stage. Early detection is needed if accurate and cost effective diagnostic methods are available. Mortality from colon cancer is theoretically preventable through screening. The Current screening method, the immunological fecal occult blood test, FOBTi, lacks sensitivity and requires dietary restriction, which impedes compliance. Moreover colonoscopy is invasive and costly, which decreases compliance, and in certain cases could lead to mortality. Compared to the FOBT test, a noninvasive sensitive screen that does not require dietary restriction would be more convenient. Colonoscopy screening is recommended for colorectal cancer (CRC). Although it is a reliable screening method, colonoscopy is an invasive test, often accompanied by abdominal pain, has potential complications and has high cost, which have hampered its application worldwide.

A screening approach that uses the relatively stable and nondegradable microRNA molecules when extracted from either the noninvasive human stool, or the semi-invasive blood samples by available commercial kits and manipulated thereafter, would be more preferable than a transcriptomic messenger (m)RNA-, a mutation DNA-, an epigenetic-or a proteomic-based test. That approach utilizes reverse transcriptase (RT), followed by a modified quantitative real-time polymerase chain reaction (qPCR). To compensate for exosomal miRNAs that would not be measured, a parallel test could be performed on stool or plasma’s total RNAs, and corrections for exosomal loss are made to obtain accurate results. Ultimately, a chip would be developed to facilitate diagnosis, as has been carried out for the quantification of genetically modified organisms (GMOs) in foods. The gold standard to which the miRNA test is compared to is colonoscopy. If laboratory performance criteria are met, a miRNA test in human stool or blood samples based on high throughput automated technologies and quantitative expression measurements currently employed in the diagnostic clinical laboratory, would eventually be advanced to the clinical setting, making a noticeable impact on the prevention of colon cancer.