Guizhen Lyu and Dongbing Li* Pages 1 - 14 ( 14 )
Background: The presence of microRNA-217 (miR-217) has been observed across various malignancies. However, its specific contribution to uterine corpus endometrial carcinoma (UCEC) is yet to be fully understood.
Objective: We aimed to explore the role of miR-217 in UCEC.
Methods: Clinical and genomic data, alongside prognostic insights, for UCEC patients were sourced from the TCGA repository. A suite of statistical tools, including the Kruskal-Wallis test, Wilcoxon sign-rank test, and logistic regression, was deployed to scrutinize the correlation between miR-217 levels and clinical profiles. The Kaplan-Meier method was applied to chart survival curves, thereby assessing the prognostic implications of miR-217 levels and its target genes in UCEC. TargetScan, PicTar, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to uncover the functional envelope of miR-217 target genes. An immune infiltration analysis provided further context to the role of miR-217 in immune modulation. We validated the expression of miR-217 in cell lines.
Results: miR-217 demonstrates atypical expression across a spectrum of cancers, including UCEC. The expression of miR-217 in the Mixed&Serous subtypes of UCEC is significantly higher than that in the Endometrioid subtype (p = 0.008). The presence of miR-217 is associated with adverse impacts on overall survival (OS) and disease-specific survival (DSS) in UCEC patients, with hazard ratios (HR) of 1.55 (95% CI: 1.00-2.38, p = 0.048) and 2.05 (95% CI: 1.19-3.53, p = 0.010), indicating statistical significance. The prognostic significance of miR-217 in UCEC is highlighted by its status as a standalone indicator of patient outcomes. Diminished expression of genes targeted by miR-217, such as BCL2, DYRK1A, IGF1R, NDN, and NHS, is correlated with diminished OS in UCEC. miR-217 is intricately involved in the pathogenesis of UCEC, potentially through involvement in pathways like the AMPK signaling and FoxO signaling pathways. The expression of miR-217 in UCEC is significantly correlated with the infiltration level of some immune cells. Notably, in cell lines derived from UCEC, miR-217 expression is markedly increased.
Conclusion: The up-regulation of miR-217 is strongly linked to an adverse prognosis in UCEC patients, suggesting its potential as a prognostic biomarker and a predictor of immunotherapy response in UCEC patients.
UCEC, miRNA-217, prognosis, target genes, immune infiltration, FoxO signaling pathway.