Comprehensive miRNA profiling of surgically staged endometrial cancer

OBJECTIVE: We sought to determine a microRNA (miRNA) profile of surgically staged endometrial cancers. STUDY DESIGN: RNA was extracted from archival primary endometrial cancers, and an miRNA profile was established using a microarray and confirmed with real-time polymerase chain reaction. Targets of differentially expressed miRNAs were explored using real-time polymerase chain reaction and Western blot in endometrial cell lines. RESULTS: Endometrial cancer has an miRNA profile distinct from normal endometrium, even in patients with stage IA grade 1 tumors. This miRNA cancer profile was able to correctly assign a specimen as a malignancy with a sensitivity of 92%. Overexpressed miRNAs were predicted to target PTEN, and transfection of cell lines with these miRNAs led to down-regulation of PTEN expression. In advanced disease, an miRNA pattern distinct from early-stage disease was seen, and overexpression of mir-199c predicted improved cancer survival in this population. CONCLUSION: Endometrial cancer has a distinct miRNA profile, and miRNAs can be used as a predictive biomarker.