Circulating serum miRNAs as diagnostic markers for colorectal cancer

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide, being the second in females and the third in males with 1.2 million annual new cases worldwide. It has been previously addressed that patients with inflammatory bowel disease (IBD) are usually associated with an increased risk of progression to epithelial dysplasia and CRC. The miRNAs represent an interesting class of small noncoding RNAs that act as posttranscriptional regulators of gene expression through binding to the 3`untranslated regions (UTR) of the target mRNAs and promoting mRNA degradation or translational repression. Cumulative evidence indicates that some miRNAs can behave either as oncomirs or tumor suppressor genes in the cascade of CRC .Therefore, they possess the potentiality to be used as diagnostic, prognostic or therapeutic tumor markers. Our study highlighted the role of aberrant miRNAs expressions in the development and progression of CRC cases the expression levels of 14 miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array at different stages of colorectal carcinogenesis cascade. The study involved two sample sets:  1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and  2- a validation set which included 100 CRC patients. The rational for selection of studied 14 miRNAs was based on prior references which illustrated their role in colorectal carcinogenesis (S1 table). The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively