CD248 Cleaved Form in Human Colorectal Cancer Stroma: Implications for Tumor Behavior and Prognosis

CD248 (endosialin/tumor endothelial marker 1) is upregulated in cancer, including colorectal cancer (CRC), but its exact role in tumor progression remains to be elucidated. Previous studies have shown that the extracellular domain of CD248 mediates the interaction between tumor cells and extracellular matrix proteins and that interfering with this interaction may reduce tumor invasion and migration activities. We have examined the expression of CD248 in 117 human CRC samples by immunohistochemistry and investigated the association with various clinicopathologic features, including the occurrence of metastasis, intratumoral immune cell density and overall survival. Of the 117 specimens analyzed, 76.1% (89/117) exhibited CD248-high stromal expression, whereas 23.9% (28/117) demonstrated CD248-low stromal expression. Interestingly, we detected the presence of a cleaved form of CD248, which appears to accumulate in the stromal extracellular matrix. A higher metastasis rate (lymph node and distant) was observed in the CD248-low group (21/28, 75.0% vs 44/89, 49.4%; P = .02). In addition, CD248-low tumors had fewer CD163-positive macrophages and FoxP3-positive regulatory T cells (P < .05) with no significant difference in CD8-positive T-cell infiltration and PD-L1 expression between the groups (P > .05). Finally, overall survival was lower in CD248-low tumors than in CD248-high tumors, with 5-year survival rates of 35.7% and 57.3%, respectively (P = .01). In a multivariate analysis, the hazard ratio of CD248-low tumors vs CD248-high tumors was 1.93 (95% CI, 1.09-3.41; P = .02). Our findings suggest that CD248 stromal expression may influence the tumor microenvironment, impacting tumor behavior and prognosis, and can serve as a promising prognostic biomarker in CRC.