Detection of miR-1246, miR-23a and miR-451 in sera of colorectal carcinoma patients: a case-control study in Cairo University hospital.

Mona Salah,Mahmoud El Guibaly,Rasha Saad,Iman Shaheen,Nagwa Eid Saad,Nouran Momen,Pakinam El-Shanawany

doi:10.4314/ahs.v20i3.33

Abstract

Colorectal cancer (CRC) has high morbidity and mortality rates. Invasive techniques and other laboratory tests with variable sensitivity and specificity are currently used in diagnosis. Micro ribonucleic acids (miRNAs) have bio vital roles in cell proliferation and apoptosis. Dys-regulation of miRNAs is linked to tumour genesis. The objective of this study was to evaluate the specificity and sensitivity of serum non-invasive biomarkers (micro-RNAs), miR-1246, miR-23a, and miR-451in CRC patients. Peripheral expression of three miRNAs (miR-1246, miR-23a and miR-451) was investigated in sera of 37 CRC Egyptian patients and 30 healthy controls, using quantitative real-time polymerase chain reaction trying to reach the optimal non-invasive combination of miRNAs. Serum miR-1246 was up-regulated in sera of CRC patients compared to normal controls (fold change = 3.55; P<0.001) and showed 100% sensitivity and 80% specificity in diagnosis of CRC. Serum miR-451 was significantly down-regulated in CRC patients (fold change = -4.86; p= 0.014), whereas, miR-23a was down-regulated but this was not statistically significant. Up-regulation of miR-1246 and down-regulation of miR-451 in the sera of primary CRC Egyptian patients were confirmed with high sensitivity and specificity. Large-scale studies on a wider spectrum of miRNAs in Egyptian CRC patients are needed.

Highlights

Cancer, especially colorectal cancer (CRC), is considered as a major public health problem all over the world, with higher rates of both morbidity and mortality in low income countries that could be attributed to late presentation and the need of invasive diagnostic techniques in addition to the expensive long therapeutic modalities[1,2,3].Other laboratory tests with variable sensitivity and specificity including occult blood in stool, Carcino-embryonic Antigen (CEA) and Cancer Antigen (CA 19-9) are used in the diagnosis of CRC4-6
The current study aimed to investigate three Micro ribonucleic acids (miRNAs), other than those previously investigated in Egyptian studies trying to reach the optimal combination of miRNAs with the highest sensitivity and specificity in Colorectal cancer (CRC) diagnosis, which could be used as molecular target therapy in the future aiming to decrease the morbidity and mortality rates of Egyptian CRC patients
Elevated serum level of CEA was detected in 27 CRC patients (73%) with a mean of10.76 ± 5.5 ng/dl, while CA 19-9 was elevated in 23 CRC patients (62.2%) with a mean of 64.85 ± 37.5 U/ml .Nine cases (24.3%) were stage II, and 28 cases (75.7%) had stage III colorectal carcinoma according to TNM staging system

Summary

Introduction

Especially colorectal cancer (CRC), is considered as a major public health problem all over the world, with higher rates of both morbidity and mortality in low income countries that could be attributed to late presentation and the need of invasive diagnostic techniques in addition to the expensive long therapeutic modalities[1,2,3].Other laboratory tests with variable sensitivity and specificity including occult blood in stool, Carcino-embryonic Antigen (CEA) and Cancer Antigen (CA 19-9) are used in the diagnosis of CRC4-6. Micro ribonucleic acids (miRNAs) are short single stranded non coding RNA with an average length of twenty nucleotides. They have been linked to cell proliferation,differentiation and apoptosis[7]. The objective of this study was to evaluate the specificity and sensitivity of serum non-invasive biomarkers (micro-RNAs), miR-1246, miR-23a, and miR-451in CRC patients. Methods: Peripheral expression of three miRNAs (miR-1246, miR-23a and miR-451) was investigated in sera of 37 CRC Egyptian patients and 30 healthy controls, using quantitative real-time polymerase chain reaction trying to reach the optimal non-invasive combination of miRNAs. Results: Serum miR-1246 was up-regulated in sera of CRC patients compared to normal controls (fold change = 3.55; P< 0.001) and showed 100% sensitivity and 80% specificity in diagnosis of CRC.

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Results

Conclusion