الفهرس 
Introduction
Chapter I: Colorectal CarcinomaOnly 14 pages are availabe for public view
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Abstract
The aim of this study was to assess the role of plasma miRNA 21 and miRNA 92-a in diagnosis of CRC and its precancerous lesions namely CRA and UC and if there are possible correlation between plasma miRNA expression levels and CRC stage using real-time RT-PCR. The study was comparative cross-sectional on 115 subjects who attended Gastroenterology Endoscopy Unit, Aswan University Hospital from May 2016 till May 2019 including 31 naive CRC cases staged by TNM classification, 28 advanced adenoma (>1 cm), 28 ulcerative colitis patients and 28 healthy controls. Plasma levels of miRNA 21 and miRNA 92-a were measured for all participants. In addition, full history/examination, full labs and colonoscopy with biopsy were done. Staging of tumours was done according to tumour-node-metastasis (TNM) classification using abdominal ultrasound and M.S.C.T abdomen and pelvis. Mean plasma levels of miRNA 21 and miRNA 92-a were significantly elevated (P-value <0.001) in CRC (36.8 ± 4.6, 40.8 ± 4.7) and CRA (8.8 ± 0.7, 11.1 ± 0.8) cases and ulcerative colitis (2.7 ± 0.3, 3.5 ± 0.4) compared to control (1.3 ± 0.3 , 1.25 ± 0.1). ROC curve analysis showed that, at a cut-off value ≥5.5 (AUC= 0.911), plasma miRNA 21 could discriminate CRC cases from controls with a 90.3% sensitivity and 85.7% specificity. At a cut-off value ≥7.5 (AUC = 0.851), plasma miRNA 92-a was 83.9% sensitive and 82.1% specific for detection of CRC. When combined, the sensitivity increased to 95.1% and specifity was 91.3%. Discrimination of CRA from control could be detected using plasma miRNA 21, at a cut-off value ≥3.2 (AUC = 0.643), with a sensitivity of 89.3% and specifity of 61.9%. At a cut-off value ≥4.5 (AUC= 0.678), plasma miRNA 92-a was 85.7% sensitive and 60.9% specific for detection of CRA. Moreover, a statistically significant strong positive correlation was noticed between CRC stage and the expression levels of both plasma miRNA 21 and miRNA 92-a (P-value <0.05). The study concluded that both plasma miRNA 21 and miRNA 92-a are promising biomarkers in the diagnosis of CRC and CRA and significantly correlate with CRC stage. Conclusions Plasma miRNA 21 and miRNA 92-a are promising biomarkers in diagnosis of colorectal carcinoma and adenoma. Plasma levels of miRNA 21 and miRNA 92-a are significantly higher in colorectal cancer relative to colorectal adenoma and ulcerative colitis. There is positive correlation between plasma miRNA 21 and miRNA 92-a levels and CRC stages. Recommendations Further future studies are needed on larger-scale population using a panel of miRNAs rather than demonstrate a single one to help further improve sensitivity and specifity in the diagnosis and prognosis of CRC and CRA as the main limitation of circulating miRNA is that some of them may be dysregulated in many types of cancers and therefore, serum miRNA may not be specific for CRC diagnosis. Comparative studies between miRNA expression in colonic versus extracolonic neoplasms are needed to evaluate specifity. In addition, validation studies are needed to detect possible variations in miRNA expression among diverse ethnic populations. Standardisation of miRNA detection techniques such as extraction and quantification methods techniques should be done using quality control mechanisms. Furthermore, nearly all studies until now have used RT-PCR that relies on a reference gene to serve as a control with lack of consensus on the ideal reference gene. Therefore, digital PCR (dPCR) is a promising new tool that offers absolute quantitation of miRNAs.