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Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

1
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-270, Brazil
2
International Research Center—CIPE, A.C. Camargo Cancer Center, Sao Paulo 01525-001, Brazil
3
Department of Head and Neck Surgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo/LIM-28-São Paulo, Sao Paulo 05403-000, Brazil
4
Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-160, Brazil
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Haroldo Juaçaba Hospital—Cancer Institute of Ceará, Fortaleza 60430-230, Brazil
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Molecular Carcinogenesis Program, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20230-240, Brazil
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Cesar Cals Hospital, Fortaleza 60015-152, Brazil
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School of Medicine, University of Fortaleza, Fortaleza 60811-905, Brazil
9
Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-160, Brazil
10
Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark
11
Institute of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
12
Danish Colorectal Cancer Center South, 7100 Vejle, Denmark
*
Authors to whom correspondence should be addressed.
These authors contributed equally and shared the first author.
These authors contributed equally and shared the last author.
Academic Editors: Damián García-Olmo and Rodrigo Jover
Cancers 2021, 13(7), 1493; https://doi.org/10.3390/cancers13071493
Received: 9 February 2021 / Revised: 16 March 2021 / Accepted: 22 March 2021 / Published: 24 March 2021
The detection of early-stage colorectal cancer increases the chance to prevent tumor progression and death by the disease. Colonoscopy is one sensitive screening test to detect malignant or potentially malignant lesions in the intestines. However, it has some disadvantages, including sedation requirements, increased risk of colon perforation, and bleeding. Circulating microRNAs (miRNAs) in plasma or serum from cancer patients have been investigated and described as potential diagnostic or prognostic markers. We conducted an miRNAs screening test in plasma samples from colorectal cancer patients and subjects without cancer, aiming to identify markers for the early detection of the disease. We identified and validated four miRNAs capable of distinguishing cancer from non-cancer cases. Our non-invasive diagnostic biomarkers presented high performance and are easily applicable to clinical practice.
Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC. View Full-Text
Keywords: colorectal cancer; blood; microRNA; diagnosis colorectal cancer; blood; microRNA; diagnosis
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MDPI and ACS Style

Silva, C.M.S.; Barros-Filho, M.C.; Wong, D.V.T.; Mello, J.B.H.; Nobre, L.M.S.; Wanderley, C.W.S.; Lucetti, L.T.; Muniz, H.A.; Paiva, I.K.D.; Kuasne, H.; Ferreira, D.P.P.; Cunha, M.P.S.S.; Hirth, C.G.; Silva, P.G.B.; Sant’Ana, R.O.; Souza, M.H.L.P.; Quetz, J.S.; Rogatto, S.R.; Lima-Junior, R.C.P. Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer. Cancers 2021, 13, 1493. https://doi.org/10.3390/cancers13071493

AMA Style

Silva CMS, Barros-Filho MC, Wong DVT, Mello JBH, Nobre LMS, Wanderley CWS, Lucetti LT, Muniz HA, Paiva IKD, Kuasne H, Ferreira DPP, Cunha MPSS, Hirth CG, Silva PGB, Sant’Ana RO, Souza MHLP, Quetz JS, Rogatto SR, Lima-Junior RCP. Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer. Cancers. 2021; 13(7):1493. https://doi.org/10.3390/cancers13071493

Chicago/Turabian Style

Silva, Camila M.S., Mateus C. Barros-Filho, Deysi V.T. Wong, Julia B.H. Mello, Livia M.S. Nobre, Carlos W.S. Wanderley, Larisse T. Lucetti, Heitor A. Muniz, Igor K.D. Paiva, Hellen Kuasne, Daniel P.P. Ferreira, Maria P.S.S. Cunha, Carlos G. Hirth, Paulo G.B. Silva, Rosane O. Sant’Ana, Marcellus H.L.P. Souza, Josiane S. Quetz, Silvia R. Rogatto, and Roberto C.P. Lima-Junior. 2021. "Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer" Cancers 13, no. 7: 1493. https://doi.org/10.3390/cancers13071493

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