Abstract
Although various factors may contribute to its initiation and progression, the etiology and prognostic factors of endometrial carcinoma (EC) remains not fully understood. We sought to understand the role of changes in transcriptome during the progress of EC by exploring public datasets. The aberrant expression characteristics of EC based on RNA-Seq and miRNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed. Kaplan–Meier analysis was performed to assess the relationship between differently expressed genes (DEGs) and patient survival. As a result, 320 out of 4,613 differently expressed mRNAs (DE mRNAs) and 68 out of 531 differently expressed miRNAs (DE miRNAs) with a significantly poorer survival were determined. We predicted eight paired DE miRNAs and DE mRNAs through TargetScan. Patients with three out of the eight paired low rate of miRNA/mRNA (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) expression had a significantly poorer survival. Furthermore, the simultaneous presence of these selected low miRNA/mRNA pairs occurred in most patients and resulted in a significantly poorer survival rate. Luciferase reporter assay identified that EMX1 was a direct target of miR-497. Both low expression of miR-497 and overexpression of EMX1 were significantly associated with more advanced clinicopathologic characteristics (stage, tumor status, grade, and histology) besides survival (all P values < 0.05). Multivariate analysis also demonstrated that miR-497 remained an independent prognostic variable for overall survival. In summary, we identified that a series of DE mRNAs and miRNAs, including eight paired DE miRNAs and mRNAs, were associated with survival in EC. Clinical evaluation of downregulated miR-497 and paired upregulated EMX1 confirmed the value of our prediction analysis. The simultaneous presence of low rate of these selected low miRNA/mRNA pairs (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) might have a better prediction value. Therefore, further studies are required to validate these findings.
Highlights
Endometrial cancer (EC) is one of the most prevalent gynecological malignancies in the word (Siegel et al, 2018)
We identified that low expression of miR-497 and overexpression of its potential target gene Empty Spiracles Homeobox 1 (EMX1) were both related to more advanced clinicopathologic characteristics
The RNA-Seq profile data of 543 endometrial carcinoma (EC) and 35 normal cases were downloaded from The Cancer Genome Atlas (TCGA) database along with the miRNA-seq data of 539 EC and 33 normal samples
Summary
Endometrial cancer (EC) is one of the most prevalent gynecological malignancies in the word (Siegel et al, 2018). EC is one of only two common cancers that defy the general trend of improvement in morbidity and mortality, with a worse survival rate today than in the 1970s (Siegel et al, 2018). The previous studies mainly focused on the single factor, such as differently expressed mRNAs (DE mRNAs), differently expressed miRNAs (DE miRNAs), or differently expressed long non-coding RNAs (DE lncRNAs) to find the potential etiology and prognostic factor of tumor. In this study, considering the silence effect to their target genes of miRNAs, we performed survival analysis on both DE mRNAs and DE miRNAs comparing EC and normal samples from TCGA database. We identified that low expression of miR-497 and overexpression of its potential target gene Empty Spiracles Homeobox 1 (EMX1) were both related to more advanced clinicopathologic characteristics
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