Prognostic impact of vascular CXCR4 expression in colorectal carcinoma

AIMS: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally. The CXCL12/CXCR4 signaling axis is implicated in tumor progression and metastasis; however, its clinical significance in CRC has not been fully elucidated. This study aims to evaluate the clinicopathological significance of CXCR4 expression in the vascular microenvironment of CRC. METHODS: In this study, CXCR4 expression was analyzed in 250 surgically resected primary CRC specimens using immunohistochemistry. The association between CXCR4 expression and clinicopathological features, as well as patient prognosis, was examined. Notably, CXCR4 expression was highly localized to vascular structures at the tumor invasive front, prompting further investigation of vascular CXCR4 expression. Single-cell RNA sequencing (scRNA-seq) of publicly available datasets was employed to identify the cellular origin of CXCR4 expression. RESULTS: Vascular CXCR4 positivity was detected in 37 cases (14.8%) and was significantly associated with venous invasion, lymph node metastasis, and advanced tumor stage (P = 0.001, P = 0.021, and P = 0.0496, respectively). Patients with high CXCR4 expression demonstrated significantly reduced overall survival compared with those with low expression (log-rank test, P = 0.0033). scRNA-seq analysis identified endothelial cells as the predominant source of vascular CXCR4 expression. CONCLUSIONS: These findings suggest that CXCR4 expression within tumor-associated vasculature may serve as a prognostic biomarker for CRC. High CXCR4 expression in endothelial cells is associated with aggressive tumor behavior and adverse clinical outcomes. Further studies are warranted to elucidate the mechanisms underlying these observations and to explore CXCR4 as a potential therapeutic target in CRC.