الفهرس 
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Abstract
With 2 million new cases reported in 2018 and a mortality rate of 9.2%, CRC represents a major health problem. Crosstalk between genetic and epigenetic mechanisms was documented in colorectal carcinogenesis. Different studies emphasized the impact of miRNAs in CRC development. Further, some miRNAs can distinguish with high accuracy between healthy subjects and CRC patients, and thus, can be used for screening, diagnosis, and treatment response.
Therefore, this study was designed to explore the differential expression levels of miR-21, -23a, and -27a in the sera and tissues of Egyptian CRC patients as well as evaluating the diagnostic efficacy of their circulating expression levels.
This was an observational prospective study in which 70 participants were enrolled. The examined group consisted of 35 CRC patients who were recruited from the Endemic Medicine Department, Kasr Elainy Hospitals, Cairo University between December 2017 and February 2019. CRC was confirmed by histopathological analysis of tissues. Additionally, 35 age- and sex-matched healthy volunteers were served as a control group.
Informed written consent was obtained from all participants included in the study. The study protocol was approved by the ethical committee of the National Research Centre with Registered RIP No. 17090, Giza, Egypt in agreement with The Declaration of Helsinki of 1975 revised in 2008.
All subjects were subjected to
• Full history and clinical examinations.
• Determination of relative miR-21, and -23a, and -27a expression levels in sera of healthy participants in addition to sera, cancerous tissues, and safety margins tissues of CRC patients.
The results of the study can be summarized as follows
• Compared to the control group, the circulating expression levels of miR-21, -23a, and -27a were significantly elevated in CRC patients.
• Circulating miR-21 expression level was significantly elevated in patients suffering from tumors localized in the ileum compared to those with tumors localized in sigmoid.
• The relative expression level of miR-27a in the sera of patients with ileum tumors was significantly up-regulated compared to those with sigmoid and caecum tumors.
• A borderline significant elevation in the circulating miR-23a expression level was observed in patients carrying tumors ≥5 cm in size compared to those with smaller tumors.
• MiR-23a relative expression was significantly higher in grade III tumors compared to grade I and II tumors.
• ROC curves of the circulating expression levels of miR-21, -23a, and -27a and their combinations to discriminate CRC patients from healthy controls showed that miR-21 had the strongest diagnostic value for CRC with an area under curve (AUC) of 0.893 and an optimal cut-off point of 2.29 followed by miR-23a with AUC of 0.887 at a cut-off point of 1.79. On the other hand, miR-27a showed the lowest diagnostic efficacy among the three parameters with AUC of 0.665 at a cut-off point of 1.47.
• The combination of the three miRNAs together resulted in an increase in the AUC of 0.908, while the combination of miR-21and -23a AUC of 0.905.
• There was a substantial agreement between the miR-21 and -23a expression levels, a moderate agreement between the miR-23a and -27a expression levels, and a fair agreement between the miR-21 and -27a expression levels on the absence and presence of CRC in healthy controls and patients according to the value of their cutoff points.
• The relative expression levels of miR-21, -23a, and -27a in CRC tissues were significantly up-regulated compared to the adjacent non-cancerous tissues.
• Positive significant correlations were found between the relative expression levels of the studied miRNAs in serum samples and their levels in the matched CRC tissues
Recommendations:
This study pointed out the over-expression of miR-21, -23a, and -27a in sera and cancerous tissues of Egyptian CRC patients and supported the notion of the potentiality of the circulating miR-21, and -23a expression level, alone or combined, to be used as non-invasive biomarkers for CRC diagnosis.
Future Prospective
Our future prospective is to compare the studied miRNAs expression in hepatocellular carcinoma with colorectal carcinoma.