Expression of CXCL13 in clear cell renal cell carcinoma: Assisting clinical diagnosis and exploring the malignant...

In the tumor microenvironment of clear cell renal cell carcinoma (ccRCC), chemokines play critical roles in disease progression. Among them, CXCL13 is highly expressed in multiple cancer types; however, its cell-autonomous functions and clinical relevance in ccRCC remain incompletely defined.

We first assessed the expression of CXCL13 and its receptor CXCR5 in ccRCC tissues and their association with clinicopathological characteristics using Western blot and immunohistochemical staining. Plasma CXCL13 levels in patients were measured by ELISA. For functional analysis, we overexpressed CXCL13 in 786-O cells and performed phenotypic assays to evaluate its effects on malignant behaviors, including proliferation, apoptosis, migration, and invasion. The role of CXCL13 in tumor growth was further confirmed using a xenograft mouse model. To explore the underlying mechanisms, we conducted transcriptome sequencing to identify downstream signaling pathways of the CXCL13/CXCR5 axis. Key pathway components were validated by Western blot, and rescue experiments were carried out to confirm their functional relevance.

Clinical data indicate that both CXCL13 and CXCR5 are highly expressed in ccRCC tissues and cell lines (p < 0.05), and are associated with higher grade and stage. Plasma CXCL13 expression in patients was significantly higher than in the control group (p < 0.05). Functional assays demonstrated that CXCL13 significantly promoted proliferation, migration, and invasion of ccRCC cells while inhibiting apoptosis. In vivo experiments showed CXCL13 accelerated xenograft tumor growth. Transcriptome sequencing revealed significant enrichment of the NF-κB pathway (p < 0.05). Western blotting confirmed that CXCL13 promotes phosphorylation-mediated degradation of IκBα and nuclear phosphorylation-activated p65. The NF-κB inhibitor QNZ effectively reversed the malignant phenotype induced by CXCL13 overexpression.

The CXCL13/CXCR5 axis activates the NF-κB signaling pathway through an autonomous effect in ccRCC, theoretically suggesting the formation of a positive feedback loop that drives tumor malignant progression. CXCL13 may serve as a biomarker for ccRCC and a highly promising therapeutic target.