CXCL8 Promotes the Progression of Vulvar Squamous Cell Carcinoma and Serves as a Potential Prognostic Biomarker

Background: Vulvar squamous cell carcinoma (VSCC), although rare, poses substantial clinical challenges due to frequent late-stage diagnosis, quality-of-life-impairing surgical interventions, and the availability of limited therapeutic options following recurrence. Therefore, exploration of the pathogenesis of vulvar cancer, and identification of effective therapeutic targets based on the biological pathways of disease progression, offer great value in improving patients’ survival duration and quality of life. Patients and Methods: Herein, we investigated the influence of C-X-C motif chemokine ligand 8 (CXCL8) on the proliferation of vulvar squamous cancer cells and the underlying mechanisms, as well as their influence on the prognosis of patients with VSCC. Results: Using a combination of RNA sequencing and Gene Expression Omnibus (GEO) database analysis, CXCL8 was identified as a differentially expressed gene in vulvar cancer tissue in comparison with adjacent normal tissue. Immunohistochemical analysis of selected clinical specimens revealed that CXCL8 was statistically upregulated in vulvar squamous cancer tissues in comparison with adjacent normal tissue, and this upregulation was correlated with shorter progression-free survival and overall survival. Functional assays demonstrated that CXCL8- mediated proliferation enhancement in VSCC cell lines (SW962/A431) in a dose- and time-dependent manner. Cell cycle analysis showed that exogenous CXCL8 drove a G0/G1-to-G2/M phase transition in SW962 and A431 cells. Transcriptomic profiling explored CXCL8-activated pathways, including cytokine-cytokine receptor interaction, transforming growth factor (TGF)-β signaling pathway, and tryptophan metabolism. Conclusion: These findings highlight CXCL8 as a potential prognostic biomarker for VSCC and underscore its role in driving tumor proliferation, providing a rationale for targeting CXCL8 in vulvar cancer therapy. Keywords: vulvar squamous cell carcinoma, CXCL8, proliferation, progression-free survival, overall survival