Expression and prognosis of CXCL13 in uterine corpus endometrial carcinoma based on bioinformatics analysis.

Abstract

Objective: The biological significance of the chemokine ligand C-X-C motif chemokine ligand 13 (CXCL13) may play a significant role in the pathogenesis of uterine corpus endometrial carcinoma (UCEC). This study aims to identify and verify CXCL13 with predictive value for prognosis in UCEC.

Methods: CXCL13 mRNA expression differences were analyzed using R software in three independent datasets: one each from The Cancer Genome Atlas (TCGA) and two from the Gene Expression Omnibus (GEO), namely GSE17025 and GSE106191. The correlation between CXCL13 expression and prognosis was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox analyses were utilized to construct a prognostic nomogram. Tumor Immune Estimation Resource (TIMER) and the Tumor and Immune System Interaction Database (TISIDB) were employed to assess the relationship between CXCL13 and tumor immune infiltration. Coexpressed genes with CXCL13 were identified by the Spearman correlation analysis. A CXCL13 protein-protein interaction (PPI) network was constructed with the STRING website tool and hub genes were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses were performed with the "clusterProfiler" R package. Gene set enrichment analysis (GSEA) was used to identify underlying biological mechanisms. A drug-gene interaction network was constructed in the Comparative Toxicogenomics Database (CTD).

Results: High CXCL13 mRNA expression were validated in UCEC in the above three independent datasets. High CXCL13 expression was associated with favorable prognosis in UCEC. A nomogram for predicting the 1-, 3-, and 5-year survival probability in UCEC was construct based on CXCL13 expression and other clinical parameters. The use of Spearman correlation indicated certain correlation between CXCL13 and immune cells and immune checkpoint (ICP) genes. Seven hub genes were upregulated in UCEC, namely CXCL9, IFNG, CXCL10, CXCL11, GBP5, CCL18, and GZMB. The expression and prognostic relevance of CXCL9, IFNG, GBP5, and GZMB were in accordance with CXCL13. The main biological processes enriched were cytokine-cytokine receptor interaction and chemokine signaling pathway.

Conclusions: The above comprehensive analyses suggest that CXCL13 may serve as a potential prognostic biomarker for UCEC, specifically for early-stage UCEC.