Abstract

Colorectal cancer (CRC) is the third lethal malignancy worldwide. Dysregulation of microRNAs (miRNAs) mediates several growth factors signaling pathways and induces abnormal genes expression, which leads to colorectal carcinogenesis. We aimed to comprehensively assess the expression of miRNA-200c, miRNA-203a, miRNA-223 in Egyptian CRC tissue and their corresponding serum samples and to explore if they have any potential prognostic or diagnostic value for CRC patients. A total of 195 subjects (120 CRC patients and 75 healthy controls) participated in exploration and validation sets. The relative expression of miRNA-200c, miRNA-203a, and miRNA-223 was measured in both CRC tissue and serum samples, and the expressed miRNAs were compared in different CRC grades and types and the prognostic value was evaluated. The expression levels of miRNA-200c and miRNA-203a were reduced in CRC tissue samples than adjacent noncancerous tissues. miRNA-223 level was significantly upregulated in both CRC tissue and serum samples with a positive association between them (r = 0.85, P = 0.001). The miRNA-223 can effectively discriminate CRC patients from controls and can significantly differentiate between colon and rectal cancer patients. The association between serum miRNA-223 expression and CRC development was validated in the second set and the ROC curve showed highly significant prognostic value with 90.1% sensitivity, 87% specificity, and area under the curve of 0.914 (95% confidence interval: 0.830-0.978, P = 0.0001). These results showed the association between miRNA-223 upregulation and the CRC carcinogenesis. Circulating miRNA-223 can be a potential noninvasive prognostic biomarker for Egyptian CRC patients.

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