蛋白酶激活受体1在癌旁组织中的高表达与肝癌早期患者术后预后不良相关

目的 研究蛋白酶激活受体1(PAR1)在肝细胞肝癌(HCC)及癌旁组织的表达水平,探讨其与HCC早期患者预后的相关性.方法 应用实时定量聚合酶链反应检测随机选择的41例经根治性切除的HCC早期患者癌组织及对应的癌旁组织中PAR1的mRNA表达水平,并分析其与肝细胞肝癌预后的相关性.另随机选择49例H C C早期患者组织石蜡切片做免疫组织化学染色,分析其与HCC临床病理特征及预后的相关性.计数资料比较采用卡方或Fisher精确概率法;计量资料比较用两组间比较的t检验或Wilcoxon符号秩检验;生存率的判定使用Kaplan-Meier方法,差异性使用Log-rank检验评估.结果 癌旁组织中,复发组的PAR1 mRNA表达水平明显高于非复发组(0.591±0.458比0.361±0.177,T=-2.379,P＜0.05).PAR1蛋白在癌旁组织的表达水平与肿瘤分化程度相关(P＜0.05).PAR1阳性组患者生存时间为(58.39±4.59)个月,1、3、5年累计生存率分别为90.3%、83.9%和61.8%; PAR1阴性组患者生存时间为(75.84±1.87)个月,1、3、5年累计生存率分别为100.0%、100.0%和94.1%.PAR1阳性组患者至复发时间为(51.97±4.30)个月,1、3、5年累计复发率分别为10.2%、25.2%和40.6%;阴性组患者至复发时间为(71.92±3.77)个月,1、3、5年累计复发率分别为0、5.6%和21.3%.癌旁组织PAR1蛋白阳性表达组1、3、5年总生存率明显低于阴性表达组(x2=5.297,P＜0.05),累计复发率明显高于阴性表达组(x2=4.682,P＜0.05).结论 PAR1在HCC早期患者癌旁组织中的表达与术后患者的预后密切相关,其可能参与了凝血酶介导的肝细胞肝癌的恶性侵袭行为,并可能成为判断预后的预测指标.

Abstract：

Objective To evaluate the relationship between PAR1 (Protease-Activated Receptor 1)expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection. Methods Real-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage.Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated. Results Peritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P＜0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P＜0.05). KaplanMeier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival(OS) (P＜0.05) of HCC patients and the time to recurrence (TTR) (P＜0.05). The 1,3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue. Conclusion Peritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.

High expression of thrombin receptor PAR1 in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma in early stage

Objective To evaluate the relationship between PAR1 (Protease-Activated Receptor 1)expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection. Methods Real-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage.Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated. Results Peritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P＜0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P＜0.05). KaplanMeier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival(OS) (P＜0.05) of HCC patients and the time to recurrence (TTR) (P＜0.05). The 1,3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue. Conclusion Peritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.