Alterations in the Expression of a Set of miRNAs in Endometrial Cancer and Their Correlation with Clinical Variables and the p53 Signaling Pathway

TL;DR

This study identifies specific miRNAs linked to endometrial cancer that could help in diagnosis and prognosis, especially through their connection to the p53 signaling pathway.

Contribution

The study identifies novel miRNA biomarkers (hsa-miR-182, hsa-miR-760, hsa-miR-449a) and their association with the p53 pathway in endometrial cancer.

Findings

hsa-miR-182 and hsa-miR-760 show diagnostic and prognostic relevance in endometrial cancer.

hsa-miR-449a is associated with diagnosis but not prognosis.

These miRNAs share TP53INP1 as a common target gene and show a positive correlation in advanced disease stages.

Abstract

Endometrial cancer is the fifth most common cancer worldwide, with one of the highest incidence and mortality rates. Its incidence is projected to increase 55% by 2030. Currently, the techniques used for its detection are heterogeneous and can be invasive and nonspecific. In this context, omics studies have gained relevance, providing solutions that have improved patient diagnosis and prognosis. In this study, we used data from the GSE268888 study as discovery cohort and data from the TCGA consortium as a validation cohort. Expression analyses were performed to identify miRNAs overexpressed in endometrial cancer. These miRNAs were then analyzed in relation to diagnostic and prognostic clinical variables. The target genes of these miRNAs were identified using bioinformatic tools, and functional enrichment analyses were conducted with this gene set to explore their involvement in relevant oncogenic signaling pathways. We also calculated the structural topology of the miRNA–target complexes and computed their correlation coefficients. We found that hsa-miR-182 and hsa-miR-760 had diagnostic and prognostic relevance and interacted with the p53 signaling pathway. Specifically, hsa-miR-449a was associated with diagnosis, but not with prognosis. Furthermore, we found that these miRNAs share TP53INP1 as a common target gene and estimated a high probability of complex formation, along with a positive correlation between these miRNAs and TP53INP1 in more advanced stages of the disease. These findings suggest that this miRNA signature has potential to be used as a diagnostic and prognostic biomarker and could serve as a foundation for future therapeutic strategies for endometrial cancer. However, further experimental validation is needed to confirm its clinical applicability.

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