Expression and prognostic value of EGF-like domain multiple 6 in uterine corpus endometrial carcinoma and its correlation with immune cell infiltration

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Abstract

Uterine corpus endometrial carcinoma (UCEC) represents a common malignancy affecting the female reproductive tract, distinguished by elevated rates of both morbidity and mortality. This study investigates EGF-like domain multiple 6 (EGFL6) expression as a potential diagnostic and prognostic biomarker in UCEC. RNA sequencing data along with clinical information of UCEC patients were sourced from The Cancer Genome Atlas (TCGA). Logistic regression analysis assessed correlations between EGFL6 expression and clinical features. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to evaluate EGFL6-related biological characteristics and signaling pathways. Immunohistochemistry (IHC) was performed on UCEC tissue microarrays to assess EGFL6 expression levels. Kaplan-Meier method and Cox regression analyses evaluated the prognostic significance of EGFL6. Three nomograms were developed to predict overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) probabilities at one, three, and five years following diagnosis. The expression of EGFL6 was validated through quantitative real-time PCR (RT-qPCR). Our findings demonstrate that EGFL6 is markedly overexpressed in UCEC and is associated with unfavorable clinical characteristics, including clinical stage and histological type. GO/KEGG and GSEA analyses highlighted its possible involvement in critical signaling pathways, such as MAPK and Ras signaling. Additionally, EGFL6 expression was associated with decreased immune cell infiltration, particularly regulatory T cells (Tregs) (r = -0.219, p < 0.001) and CD8 + T cells (r = -0.217, p < 0.001). Overall, EGFL6 expression is linked to poor patient prognosis. In conclusion, EGFL6 presents itself as a potential biomarker for UCEC, which could greatly influence the improvement of diagnostic and prognostic evaluations.

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