Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis

差异失调的 microRNA 作为溃疡性结肠炎肿瘤进展的新型生物标志物

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作者:Isabel Quintanilla, Gerhard Jung, Mireya Jimeno, Juan José Lozano, Julia Sidorova, Jordi Camps, Sabela Carballal, Luis Bujanda, Maria Isabel Vera, Enrique Quintero, Marta Carrillo-Palau, Miriam Cuatrecasas, Antoni Castells, Julià Panés, Elena Ricart, Leticia Moreira, Francesc Balaguer, Maria Pellisé

Discussion

UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.

Methods

In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs).

Results

Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05).

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