255P - MEX3A is a prognostic biomarker and correlates with RNA splicing and cell proliferation in endometrial cancer by analysis of RNA-seq data

Background

MEX3A is an evolutionarily conserved RNA-binding protein (RBP), of which functions and target genes in mammals remain largely unknown. Also, no previous study has shown the role of MEX3A in endometrial cancer.

Methods

We screened the differentially expressed genes (DEGs) and miRNAs (DEmiRs) between endometrial cancer samples and paired adjacent noncancerous endometrium samples with RNA-seq data. Then, we used package clusterProfiler to profile the GO and KEGG enrichment analysis of the most highly correlated genes with MEX3A, as well as the overlap genes with up-regulated DEGs. We evaluated the prognostic effect of genes using the Kaplan-Meier Plotter database. MEX3A tissue-specific expression was analyzed via the Human Protein Atlas database and TIMER. Methylation analysis was generated by MethHC and Wanderer.

Results

The volcano plot of DEmiRs showed a significant reduction in tumor suppressor miR-139 in tumor tissues compared to normal tissues. We totally identified 422 target genes of miR-139-5p using the prediction software TargetScan (7.1 version). MEX3A was one of the seven overlapping genes that we got between the miRNA target genes and the 842 up-regulated DEGs. MEX3A was significantly overexpressed in many types of tumor tissues, and interestingly, it had the highest expression in the female tissues. In addition, high MEX3A expression was significantly correlated with poor OS and progression-free survival (PFS) in endometrial cancers (OS HR = 2.07, P = 0.0021; PFS HR = 2.11, P = 0.0047). The GO analysis of top 5% most highly correlated genes with MEX3A in endometrial cancer revealed that biology processes associated with RNA splicing were mainly enriched. Simultaneously, the most enriched pathway was spliceosome, which indicated that the RBP may play an important role in the RNA splicing. Meanwhile, the MEX3A promoter region in the tumor tissue was hypomethylated compared to normal tissue. In addition, the MEX3A promotor differential methylation level is negatively correlated with MEX3A mRNA expression (corr = -0.512).

Conclusions

These findings suggest MEX3A is a potential prognostic biomarker in endometrial cancer and might play an oncogenic role as a novel cancer-critical splicing factor.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

The author has declared no conflicts of interest.