Isabel Quintanilla1,2,3, Gerhard Jung1,2,4,5, Mireya Jimeno1,6, Juan José Lozano2,7, Julia Sidorova2,7, Jordi Camps1,2, Sabela Carballal1,2,4,5, Luis Bujanda2,8, Maria Isabel Vera9, Enrique Quintero10, Marta Carrillo-Palau10, Miriam Cuatrecasas1,2,11, Antoni Castells1,2,4,5, Julià Panés1,2,4,5, Elena Ricart1,2,4,5, Leticia Moreira1,2,4,5, Francesc Balaguer1,2,4,5, Maria Pellisé1,2,4,5. 1. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 2. Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. 3. National Cancer Institute, NIH, Bethesda, Maryland, USA. 4. Department of Gastroenterology, Hospital Clinic, Barcelona, Spain. 5. Faculty of Medicine, University of Barcelona, Barcelona, Spain. 6. Departament of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 7. Bioinformatics Platform, CIBEREHD, Barcelona, Spain. 8. Department of Gastroenterology, Biodonostia Health Research Institute, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain. 9. Department of Gastroenterology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain. 10. Department of Gastroenterology, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain. 11. Department of Pathology, Hospital Clinic, Barcelona, Spain.
Abstract
INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. 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). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.
INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. 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). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.