The prognostic correlation between CD105 expression level in tumor tissue and peripheral blood and sunitinib administration in advanced hepatocellular carcinoma

摘要

Objectives: The study was designed to investigate the tumor vessel-associated CD105 expression in monocytes from tumor tissue and peripheral blood (PB) in patients with advanced hepatocellular carcinoma (HCC), in order to provide support and reference for clinical pharmaceutical therapy. Methods: A total of 50 patients with advanced HCC who were administered with sunitinib were collected. Immunohistochemistry (IHC) was utilized to assess the CD105 expression in tumor tissue, and real-time quantitative PCR (qPCR) was used to determine the mRNA expression of CD105 of monocytes in tumor tissue and PB, as well as the mRNA expression of TGF beta 1, Smad1-4 in tumor tissue. Afterwards, enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression level of TGF beta 1 and Smad1-4 in tumor tissues. Moreover, the correlation of CD105 expression with clinicopathological characteristics, overall survival (OS) and progression-free survival (PFS) was analyzed. Results: The Cd105 expression was detected both in tumor tissue and PB, and there was a correlation between them (r = 0.7791, P < 0.001). The OS and PSF were significantly increased in patients with lower expression of CD105 in tumor tissue compared to those with higher expression (10.9 vs 4.5, P < 0.001, 8.3 vs 6.15, P < 0.001). Consistently, the OS and PSF were significantly elevated in patients with lower expression of CD105 in PB than those with higher expression (10.3 vs 5.0, P < 0.001, 8.5 vs 6.3, P < 0.001). The OS and PSF were significantly enhanced in patients with lower expression of CD105 in both tumor tissue and PB compared to those with higher expression of CD105 in both tumor tissue and PB (12.4 vs 8.5, P < 0.001, 8.5 vs 6.5, P < 0.001). Both protein and mRNA expression of TGF beta 1, Smad1, Smad2 and Smad4 in patients with high CD105 expression in tumor tissue were significantly higher than those with low CD105 expression (P < 0.001), while the protein and mRNA expression of Smad3 in patients with high CD105 expression in tumor tissue were significantly lower compared to those with low CD105 expression (P < 0.001). In analysis of correlation with tumor stage, both protein and mRNA expression of TGF beta 1, Smad1, Smad2 and Smad4 in patients with stage III HCC were significantly lower than those with stage IV HCC (P < 0.001), while the protein and mRNA expression of Smad3 in patients with IV stage HCC was significantly higher in comparison to those with stage IV HCC (P < 0.001). Cox regression analysis indicated that CD105 expression in tumor tissue and PB was an independent predictive factor for the OS and PFS of advanced HCC patients who received sunitinib. Conclusions: Advanced HCC patients with lower CD105 expression in tumor tissue and PB benefited more from sunitinib administration. Moreover, CD105 expression was an independent prognostic indicator for sunitinib administration in advanced HCC, which could be used as a predictive approach for sunitinib efficacy in clinical practice.