Abstract
Background: Angiopoietins (Angs) and angiogenic microRNAs are associated with prognosis in tumors. Monocyte subsets express Ang-receptor TIE2 (TEMs) and exert pro-angiogenic properties associated with prognosis. However, little is known regarding their influence on tumor progression in human cholangiocarcinoma (CCA) Methods: We analyzed surgical specimens of intrahepatic CCA (n = 88) immunohistologically for distribution of Angs and TEMs. We tested miR targeting genes encoding Angs to be associated with tumor growth (n=44). MiRNA expression and abundance of TEMs were correlated with clinicopathologic characteristics, recurrence and patients’ survival Results: Absence of TEMs in tumor correlated with elevated CA19-9 serum levels. High Ang1 expression associated with reduced lymphangiosis carcinomatosa (all ρ<0.05). Patients characterized by invading TEMs showed a trend to reduced tumor recurrence and increased survival (ρ=0.159 and ρ=0.185). High miR-126 or low miR-128 expression was associated with improved survival (all p<0.05). In a multivariate analysis TEMs, miR-126 and low miR-128 were confirmed as independent prognosticators for survival (all p<0.05) Conclusion: TEMs define a subgroup of patients with improved tumor characteristics and prognosis. Our study provides first evidence that angiogenic miRNAs associate with survival in CCA. Besides suggested functional links between miRNA expression profiles, angiopoietins and TEMs, our data have possible clinical implications as novel diagnostic tools
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