CXCL13 as a Prognostic Biomarker and Immune Microenvironment-Associated Gene in Endometrial Carcinoma: A Multi-Omics Investigation

Immune remodeling within the tumor microenvironment (TME) influences the progression and clinical outcome of uterine corpus endometrial carcinoma (UCEC), but the contribution of chemokine-related regulatory genes remains incompletely characterized. This study aimed to evaluate the prognostic relevance of CXCL13 and its association with immune microenvironmental features in UCEC using publicly available transcriptomic and single-cell datasets. RNA-sequencing profiles and clinical annotations from 589 UCEC cases in The Cancer Genome Atlas (TCGA) were analyzed to assess TME composition using ESTIMATE (Estimation of Stromal and Immune cells in MAlignant Tumours using Expression data) and CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts), followed by survival analysis, differential gene expression analysis, protein–protein interaction network construction, Cox regression, and gene set enrichment analysis. A public single-cell RNA-sequencing dataset from the Gene Expression Omnibus (GEO; GSE173682) was further used to infer the cellular sources of CXCL13. Elevated CXCL13 expression was associated with favorable overall survival and enrichment of immune-activation pathways. CIBERSORT-based analysis indicated that high CXCL13 expression correlated with increased estimated fractions of CD8+ T cells and plasma cells, together with transcriptional features related to tertiary lymphoid structure-associated immune activation, whereas several immunosuppressive cell populations showed lower estimated abundance. Single-cell analysis suggested that CXCL13 was mainly expressed by follicular helper T cells and exhausted CD8+ T cells. These findings indicate that CXCL13 may serve as a prognostic biomarker associated with an immune-active TME in UCEC. Further histological, spatial, and functional validation is warranted to confirm its mechanistic role and translational potential.