Identification and Validation of MicroRNA Profiles in Fecal Samples for Detection of Colorectal Cancer

被引:65
作者
Duran-Sanchon, Saray [1 ]
Moreno, Lorena [1 ]
Auge, Josep M. [2 ]
Serra-Burriel, Miquel [3 ]
Cuatrecasas, Miriam [4 ,5 ]
Moreira, Leticia [1 ]
Martin, Agatha [1 ]
Serradesanferm, Anna [6 ]
Pozo, Angels [6 ]
Costa, Rosa [1 ]
Lacy, Antonio [7 ]
Pellise, Maria [1 ]
Jose Lozano, Juan [8 ]
Gironella, Meritxell [1 ]
Castells, Antoni [1 ]
机构
[1] Univ Barcelona, Hosp Clin Barcelona, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi i Sunyer,Gastroenter, Barcelona, Catalonia, Spain
[2] Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer, Biochem & Mol Genet Dept, Barcelona, Catalonia, Spain
[3] Univ Pompeu Fabra, Ctr Res Hlth & Econ, Barcelona, Catalonia, Spain
[4] Hosp Clin Barcelona, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi i Sunyer, Pathol Dept, Barcelona, Catalonia, Spain
[5] Hosp Clin Barcelona, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi i Sunyer, Tumour Bank Biobank, Barcelona, Catalonia, Spain
[6] Hosp Clin Barcelona, Prevent Med & Hosp Epidemiol Dept, Barcelona, Catalonia, Spain
[7] Univ Barcelona, Hosp Clin Barcelona, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi i Sunyer,Gastrointes, Barcelona, Catalonia, Spain
[8] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Bioinformat Platform, Barcelona, Catalonia, Spain
关键词
Biomarker; FIT; miR-421; miR-130b; NONINVASIVE BIOMARKER; TASK-FORCE; STOOL; NEOPLASIA; FECES; COLONOCYTES; COLONOSCOPY; BIOGENESIS; DIAGNOSIS; MODELS;
D O I
10.1053/j.gastro.2019.10.005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Screening for colorectal cancer (CRC) is effective in the population at average risk. The most extended strategy in organized programs involves the fecal immuno-chemical test, which is limited by low sensitivity for the detection of advanced adenomas (AAs). We aimed to identify microRNA (miRNA) signatures in fecal samples that identify patients with AAs or CRC and might be used in noninvasive screening. METHODS: Our study comprised 4 stages. In the discovery phase, we performed genome-wide miRNA expression profiling of 124 fresh, paired colorectal tumor and nontumor samples (30 CRC; 32 AAs) from patients in Spain. In the technical validation stage, miRNAs with altered expression levels in tumor vs nontumor tissues were quantified by reverse-transcription polymerase chain reaction in fecal samples from a subset of patients included in the discovery phase (n = 39) and individuals without colorectal neoplasms (controls, n = 39). In the clinical validation stage, the miRNAs found to be most significantly up-regulated by quantitative reverse transcription polymerase chain reaction analysis were measured in an independent set of fecal samples (n = 767) from patients with positive results from fecal immunochemical tests in a CRC screening program. Finally, we developed a model to identify patients with advanced neoplasms (CRCs or AAs) based on their miRNA profiles, using findings from colonoscopy as the reference standard. RESULTS: Among 200 and 324 miRNAs significantly deregulated in CRC and AA tissues, respectively, 7 and 5 of these miRNAs were also found to be deregulated in feces (technical validation). Of them, MIR421, MIR130b-3p, and MIR27a-3p were confirmed to be upregulated in fecal samples from patients with advanced neoplasms. In our model, the combination of fecal level of MIR421, MIR27a-3p, and hemoglobin identified patients with CRC with an area under the curve (AUC) of 0.93, compared with an AUC of 0.67 for fecal hemoglobin concentration alone. CONCLUSIONS: We found that increased levels of 2 miRNAs and hemoglobin in feces can identify patients with AAs or CRC more accurately than fecal hemoglobin concentration alone. Assays for these miRNAs might be added to fecal tests for the detection of CRC or AAs.
引用
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页码:947 / +
页数:15
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