Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer

The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. The study involved two sample sets: 1- a training set which included 90 patients with...

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Published in:	PloS one Vol. 11; no. 5; p. e0154130
Main Authors:	Zekri, Abdel-Rahman N, Youssef, Amira Salah El-Din, Lotfy, Mai M, Gabr, Reham, Ahmed, Ola S, Nassar, Auhood, Hussein, Nehal, Omran, Dalia, Medhat, Eman, Eid, Salam, Hussein, Marwa Mahmoud, Ismail, Maha Yahia, Alenzi, Faris Q, Bahnassy, Abeer A
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 02-05-2016 Public Library of Science (PLoS)
Subjects:	Adult Analysis Biological markers Biology Biology and life sciences Biomarkers Biomarkers, Tumor - blood Blood serum Cancer Carcinogenesis Carcinogens Care and treatment Case-Control Studies Cell cycle Cell growth Colonic Polyps - blood Colonic Polyps - genetics Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - blood Colorectal Neoplasms - diagnosis Colorectal Neoplasms - genetics Data analysis Data processing Deoxyribonucleic acid Diagnosis Diagnostic systems DNA DNA damage Female Gene expression Health risk assessment Humans Identification methods Immunology Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - blood Inflammatory Bowel Diseases - genetics Intestine Male Medical diagnosis Medicine Medicine and Health Sciences Metastasis MicroRNA MicroRNAs MicroRNAs - blood Middle Aged miRNA Oncology Pathology Patients Polyps Reverse Transcriptase Polymerase Chain Reaction ROC Curve Training Virology Cairo Egypt Egypt
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Summary:	The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. 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. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following 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. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04). Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. 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.
Bibliography:	Conceived and designed the experiments: ANZ. Performed the experiments: MML RG OSA. Analyzed the data: ANZ ASY OSA SE AN. Contributed reagents/materials/analysis tools: DO NH MMH MYI FQA EM. Wrote the paper: ASY AN MML AAB. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0154130