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

Camila Meirelles S. Silva*, Mateus C. Barros-Filho, Deysi Viviana T. Wong, Julia Bette H. Mello, Livia Maria S. Nobre, Carlos Wagner S. Wanderley, Larisse T. Lucetti, Heitor A. Muniz, Igor Kenned D. Paiva, Hellen Kuasne, Daniel Paula P. Ferreira, Maria Perpétuo S.S. Cunha, Carlos G. Hirth, Paulo Goberlânio B. Silva, Rosane O. Sant’ana, Marcellus Henrique L.P. Souza, Josiane S. Quetz, Silvia R. Rogatto*, Roberto César P. Lima-Junior

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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.

Udgave nummer7
Antal sider18
StatusUdgivet - 24. mar. 2021

Bibliografisk note

Funding Information:
Funding: R.C.P. Lima-Júnior received a research grant from REBRATS (Rede Brasileira de Avaliação de Tecnologias em Saúde—Support for Strategic Research for the Health System by the Brazilian Health Technology Assessment Network (REBRATS); theme “Aging and Chronic Diseases”, grant number: 400132/2016-8); CNPq (Conselho Nacional de Desenvolvimento Científico e Tec-nológico, grant number: 310568/2017-0), FUNCAP (Fundação Cearense de Apoio ao Desenvolvi-mento Científico e Tecnológico, grant number: PR2-0101-00054.01.00/15) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, grant number CAPES-PROEX 23038.015378/2016-51). R.C.P. Lima-Júnior is a Productivity Research Fellow supported by CNPQ. S.R. Rogatto acknowledges support from The Danish Colorectal Cancer Center South and Research Council Lillebaelt Hospital, Denmark.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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