Chen Gang, Luo Dian-Zhong, Wang Yun, Liao Zhi-Ling, Zhang Mei-Yan
Department of Pathology, Guangxi Medical University, Nanning 530021, China.
Zhonghua Bing Li Xue Za Zhi. 2007 Feb;36(2):113-7.
To study the expression of decoy receptor 3 (DcR3) and its relationship with apoptosis and prognosis in hepatocellular carcinoma (HCC).
The expression of DcR3 protein in 43 cases of HCC and 16 cases of non-cancerous liver (including cirrhotic liver tissue and normal liver tissue adjacent to cavernous hemangioma) was studied by immunohistochemistry (using EnVision method). The status of apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Statistic analysis was carried out to assess the correlation between DcR3 expression, apoptotic index (AI) and clinicopathologic parameters.
DcR3 protein was expressed in the cytoplasm of HCC cells. The positivity rate of DcR3 in HCC was 74.42% (32/43), which was significantly higher than that in the non-cancerous group (43.75%, P < 0.05). The positivity rate of DcR3 in HCC with metastasis detected within 20 months of diagnosis was 100% (22/22). This was significantly higher than that in HCC without metastasis (52.94%, P < 0.01). The DcR3 expression in HCC also correlated with serum alpha-fetoprotein level (r = 0.444, P < 0.01) and presence of tumor embolus in portal vein (r = 0.414, P < 0.01). However it had no relationship with the patient's age, sex, cirrhotic status, liver capsule invasion, number of tumor nodules and histologic differentiation (P > 0.05). The AI in HCC (0.78 +/- 0.64)% was significantly lower than that in the non-cancerous group [(3.32 +/- 1.81)%, P < 0.01]. The AI in clinical TNM stage I and II tumors (1.03 +/- 0.69)% was significantly higher than that in stage III and IV tumors [(0.52 +/- 0.48)%, P < 0.01]. The AI in HCC without metastasis (1.10 +/- 0.72)% was significantly higher than that in HCC without metastasis [(0.44 +/- 0.27)%, P < 0.05]. The AI correlated with serum alpha-fetoprotein level (r = -0.468, P < 0.01), presence of tumor embolus in portal vein (r = -0.434, P < 0.01) and liver capsule invasion (r = -0.331, P < 0.05). On the other hand, it had no relationship with patient's age, sex, cirrhotic status, number of tumor nodules and histologic differentiation (P > 0.05). The AI in DcR3-positive group (including both HCC and non-cancerous tissues) was significantly lower than that in DcR3-negative group (P < 0.01).
The expression of DcR3 in HCC correlates with apoptosis of tumor cells and may play a crucial role in tumor pathogenesis and progression. DcR3 protein expression and AI may also serve as important biologic indicators in predicting prognosis of HCC.
研究诱饵受体3(DcR3)在肝细胞癌(HCC)中的表达及其与细胞凋亡和预后的关系。
采用免疫组织化学法(EnVision法)研究43例HCC及16例非癌肝组织(包括肝硬化肝组织及海绵状血管瘤旁正常肝组织)中DcR3蛋白的表达。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)技术评估细胞凋亡状态。进行统计学分析以评估DcR3表达、凋亡指数(AI)与临床病理参数之间的相关性。
DcR3蛋白在HCC细胞胞质中表达。HCC中DcR3的阳性率为74.42%(32/43),显著高于非癌组(43.75%,P<0.05)。诊断后20个月内检测到有转移的HCC中DcR3的阳性率为100%(22/22),显著高于无转移的HCC(52.94%,P<0.01)。HCC中DcR3表达还与血清甲胎蛋白水平(r=0.444,P<0.01)及门静脉瘤栓的存在(r=0.414,P<0.01)相关。但与患者年龄、性别、肝硬化状态、肝包膜侵犯、肿瘤结节数量及组织学分化无关(P>0.05)。HCC中的AI(0.78±0.64)%显著低于非癌组[(3.32±1.81)%,P<0.01]。临床TNM分期I和II期肿瘤的AI(1.03±0.69)%显著高于III和IV期肿瘤[(0.52±0.48)%,P<0.01]。无转移的HCC中的AI(1.10±0.72)%显著高于有转移的HCC[(0.44±0.27)%,P<0.05]。AI与血清甲胎蛋白水平(r=-0.468,P<0.01)、门静脉瘤栓的存在(r=-0.434,P<0.01)及肝包膜侵犯(r=-0.331,P<0.05)相关。另一方面,与患者年龄、性别、肝硬化状态、肿瘤结节数量及组织学分化无关(P>0.05)。DcR3阳性组(包括HCC和非癌组织)的AI显著低于DcR3阴性组(P<0.01)。
HCC中DcR3的表达与肿瘤细胞凋亡相关,可能在肿瘤发病机制和进展中起关键作用。DcR3蛋白表达和AI也可能作为预测HCC预后的重要生物学指标。