miR-194 as a Predictor for Adenoma Recurrence in Patients with Advanced Colorectal Adenoma after Polypectomy

Abstract

microRNAs (miRNA) are promising predictors in colorectal cancer (CRC). We investigated whether miRNAs could predict adenoma recurrence in patients with advanced colorectal adenoma (ACRA) after polypectomy. miRNA expression profiling was performed by miRNA microarray to identify recurrencerelated miRNAs. Candidate miRNAs extracted from formalin-fixed paraffin-embedded blocks of patients with ACRA were measured using real-time PCR. Logistic regression analysis was conducted to investigate whether validated miRNA expression profiles were independent from other known adenoma recurrence risk factors. The prognostic values of six miRNAs and three independent risk factors were assessed by the area under the receiver operating characteristic (ROC) curve analysis. The expressions of six candidate miRNAs were significantly decreased from levels in normal colorectal tissue compared with ARCA with adenoma recurrence (RACRA) in this retrospective cohort. However, only miRNA (miR)-194 emerged as a practical predictor. The sensitivity and specificity of miR-194 as a predictor were 71.0% and 78.0%, respectively, at a cutoff value of 0.1311 in the retrospective cohort. Sensitivity and specificity were 76.1% and 77.2%, respectively, in the prospective cohort using the same cutoff value. Low expression levels of miR-194, adenoma size !2 cm, and !3 adenomas were independent risk factors for adenoma recurrence. Moreover, low expression of miR-194 was a better predictor of adenoma recurrence than the adenoma size and numbers according to ROC curve analysis. miR-194 may be an independent predictor for adenoma recurrence in patients with ACRA after polypectomy. Cancer Prev Res; 7(6); 607-16. Ó2014 AACR.

MicroRNA Signatures of Colonic Polyps on Screening and Histology

“…Furthermore, the authors noted that decreased levels of miR-194 expression was associated with tumor size, differentiation, and TNM stage (33). In a recent study, low expression of miR-194, adenoma size >2 cm, and >3 adenomas were shown to have independent risk factors for adenoma recurrence (34). In particular, it was found that in a 158-patient cohort, the sensitivity and specificity of miR-194 as a predictor were 71% and 78%, respectively, at a cut-off value of 0.13.…”

MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway

“…15 In CRC, miR-194 has been reported to be downregulated in colon tissues 16 and can predict adenoma recurrence. 17 Sundaram 18 found that miR-194 could promote angiogenesis and facilitate tissue repair by targeting thrombospondin-1. However, the functions and mechanisms of miR-194 involved in CRC are not fully elucidated and the therapeutic application of miR-194 has not been reported.…”

The Dual Role of MicroRNAs in Colorectal Cancer Progression

“…MiR-194 was frequently decreased in CRC, with this level closely associated with the overall survival of patients and obviously associated with tumor size, as well as the tumor node metastasis (TNM) stage that is involved with cell proliferation, colony formation, promoted G0/G1 arrest, and induced cell apoptosis through negative regulation of the MAP4K4/c-Jun/MDM2 or PDK1/AKT2/XIAP signaling pathway, and acts as an tumor inhibitor in CRC, but not related to lymphatic invasion and distant metastasis [ 65 , 66 ]. In addition, the low expression levels of miR-194 in patients, correlated with advanced colorectal adenoma (ACRA) after polypectomy, used independently as a better predictor for adenoma recurrence [ 67 ]. MiR-194 target genes display concordant expression profiles with oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) involved in limiting cell proliferation and migration, reducing xenograft growth, attenuating cell migration, suppressing EMT, and promoting anticancer drug sensitivity in CRC [ 68 ].…”