Identification of micro-RNA expression profile related to recurrence in women with ESMO low-risk endometrial cancer

Abstract

Background: Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. Methods: MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R-), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. Results: The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R- women. Women with a micro-RNA-184 fold change<0.083 were more likely to show recurrence (n=6; 66%) compared to those with a micro-RNA-184 fold change>0.083 (n=1; 8%), p=0.016. Women with a micro-RNA-196 fold change<0.56 were more likely to show recurrence (n=5; 100%) compared to those with a micro-RNA-196 fold change>0.56 (n=2; 13%), p=0.001. Conclusions: These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.