RAIL Receptors in Hepatocellular Carcinoma
نویسندگان
چکیده
Download pose: After the advent of targeted therapies for hepatocellular carcinoma (HCC), much work is done to provide a comprehensive description of the different signaling pathways contributing survival and proliferation in this tumor. Apoptotic signaling mediated by tumor necrosis factor– apoptosis-inducing ligand (TRAIL) represents an important mechanism of tumor surveillance, but portance in the development of HCC is not known. We thus investigated the cellular distribution e prognostic importance of TRAIL receptors in HCC. erimental Design: Immunohistochemical staining for TRAIL receptors was evaluated in HCC s and in matched surrounding nontumor tissues of 157 HCC patients treated with liver transplanor partial hepatectomy. Survival was analyzed in 93 patients who underwent partial hepatectomy. ults: The fraction of HCC samples with positive membrane staining for TRAIL receptor AIL-R1) and 2 (TRAIL-R2) was 1.4and 2.7-fold lower compared with that of hepatocytes from nding tissues (P = 0.01). Loss of either TRAIL-R1 or TRAIL-R2, as confirmed by a multivariate is, significantly worsened 5-year survival of HCC patients {survival, 27% versus 52% and 15% 43%; hazard ratio (HR), 2.3 [95% confidence interval (CI), 1.1-4.4] and 2.4 (95% CI, 1.1-5.2), tively}. Loss of both TRAIL receptors further decreased survival of patients [HR, 5.72 (95% CI, .5) versus double-negative staining; P = 0.001], indicating an additive effect on survival of -R1 and TRAIL-R2. clusions: This pilot study suggests that loss of TRAIL receptors is a frequent feature of HCCs and ependent predictor of survival in patients undergoing partial hepatectomy. Future therapeutic an ind protocols are likely to profit from the characterization of their expression and cellular distribution. Clin Cancer Res; 16(22); 5529–38. ©2010 AACR.
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تاریخ انتشار 2010