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Prognostic Significance and Primary-Metastatic Differences in VASH1 Expression, CD34-Defined Microvessel Density, and
Oktay Halit Aktepe1, Rezan Berkay Izgor2, Ozlem Aydin Isak3
1Department of Medical Oncology, Dokuz Eylul University, Izmir 35330, Türkiye.
Abstract:
This study evaluated the prognostic significance of vasohibin-1 (VASH1) expression, cluster of differentiation 34 (CD34)-defined microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression, as well as the differences in these parameters between primary and metastatic colorectal cancer (CRC) lesions. Tissue microarrays were used to quantify VASH1 and VEGF expression and CD34-defined MVD. Receiver operating characteristic (ROC) analysis identified optimal cut-off values for overall survival (OS). Correlations among markers were analyzed with Spearman's test, paired tissue comparisons by the Wilcoxon signed-rank test, and survival outcomes by Kaplan-Meier and Cox regression analyses. The study included 144 CRC patients (median age: 60 years; 59% male). ROC analysis determined optimal thresholds of 6 for VASH1 (area under the curve [AUC]: 0.79, 95% confidence interval [CI]: 0.72-0.87), 37 for CD34-defined MVD (AUC: 0.76, 95% CI: 0.68-0.84), and 6 for VEGF (AUC: 0.67, 95% CI: 0.58-0.76). Patients with high VASH1 expression, high CD34-defined MVD, and high VEGF expression had significantly shorter OS compared with their corresponding low-marker groups (VASH1, p < 0.001; CD34-defined MVD, p < 0.001; VEGF, p = 0.007). Among the 45 patients with paired primary and metastatic samples, metastatic lesions showed significantly lower VASH1 and VEGF expression and lower CD34-defined MVD than matched primary tumors, with median values decreasing from 6.0 to 4.0 for VASH1 (p = 0.002), from 4 to 3 for VEGF (p < 0.001), and from 32 to 27 for CD34-defined MVD (p < 0.001). In multivariate analysis, high VASH1 expression (hazard ratio [HR]: 2.05, 95% CI: 1.01-4.20, p = 0.048) and high CD34-defined MVD (HR: 2.12, 95% CI: 1.15-3.89, p = 0.015) remained independent predictors of poor OS. High VASH1 expression and high CD34-defined MVD were independent adverse prognostic factors for OS in CRC. Lower angiogenesis-related marker levels in metastatic lesions suggest heterogeneity in tumor angiogenesis. External validation is required before clinical application.
