Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations

Abstract

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor

“…In a previous study we have investigated a possible correlation between miRNA expression and CTNNB1 mutations in sporadic DTs [17]. In this study we aim to find out the differences in miRNA expression between sporadic and FAP-associated DTs.…”

“…By retrieving clinical data of our previous study [17], 27 consecutive patients with histologically proved DT (20 with sporadic DT and 7 with FAP-associated DT), undergone surgery in our surgical unit between 1999 and 2015, were evaluated. Patients with previous history of cancer, pretreatment with non-steroidal anti-inflammatory drugs, chemotherapy, hormonotherapy or radiotherapy were excluded.…”

“…Clinical and pathologic characteristics of the patients are described in Table 3. The analysis was carried out on formalin-fixed paraffin-embedded (FFPE) tumor specimens obtained by the Pathology Department after immunohistochemical analysis as explained elsewhere [17]. Consecutive FFPE tissue sections (4-μm thick) obtained from the same block of each patient, were cut and processed for miRNAs and mRNAs identification.…”

“…We identified the differentially expressed miRNAs in two DT forms by microarray (2,080 mature miRNAs) considering 7 FAP-associated and 20 sporadic DT patients. The microarray analysis has been described previously [17].…”

“…Nineteen miRNAs showing different levels between the two forms of DT were analyzed by reverse transcription (RT) and by quantitative PCR (qPCR) methods to validate the microarray data [17]. For RT-qPCR were used miRCURY LNAUniversal RT microRNA PCR and miRCURY LNA SYBR Green PCR Kits (Exiqon-Qiagen, Vedbaek, Denmark), respectively.…”