钙敏感受体和E钙粘蛋白在肺腺癌中的表达及其临床意义

摘要

Objective: It was reported that calcium sensing receptor, a widely expressed G protein-coupled receptor, could stimulate cell differentiation and proliferation. But in malignant tumors, loss of calcium sensing receptor expression was associated with tumorigenesis, metastasis, and progression. Recent studies indicated that calcium sensing receptor could promote the expression of E-cadherin which was considered as a tumor suppressor. However, in human lung adenocarcinoma, the importance of calcium sensing receptor and E-cadherin has not been suffciently investigated.Methods: Expression levels of calcium sensing receptor and E-cadherin in paraffn sections from 117 resected lung adenocarcinoma patients were evaluated by immunohistochemistry. We analyzed the correlation between our target proteins and clinical variables. Clinical signiifcance was analyzed by multivariate Cox regression analysis, Kaplan-Meier curve and log-rank test.Results: Expression of calcium sensing receptor in lung adenocarcinoma tissue was signiifcantly lower than in normal sample (P=0.003). Kendall taub analysis showed that, in lung adenocarcinoma sample, the expression of calcium sensing receptor positively correlated with high level of E-cadherin (P<0.001). Lung adenocarcinoma patients with strong expression of calcium sensing receptor (P=0.034) or E-cadherin (P=0.001) had a longer overall survival. Multivariate Cox proportional hazards model analysis showed that the combined marker was an independent prognostic indicator of overall survival (HR =0.440, 95 CI, 0.249~0.779,P=0.005).Conclusion: We identified calcium sensing receptor as a new prognostic biomarker in lung adenocarcinoma. These results also suggested that calcium sensing receptor may become a new therapeutic target of lung adenocarcinoma.%目的：据报道钙敏感受体–一个广泛表达的G蛋白偶联受体，可以促进细胞的分化和增殖。但是在恶性组织中，钙敏感受体表达的减少与肿瘤的发生、转移和进展相关。目前的研究表明钙敏感受体可以促进E钙粘蛋白的表达，而E钙粘蛋白被认为是一种肿瘤抑制蛋白。然而，钙敏感受体和E钙粘蛋白在肺腺癌中的研究鲜有报道。方法：用免疫组织化学法分别检测117例肺腺癌石蜡切片中钙敏感受体及E钙粘蛋白的表达水平。分析目标患者和临床特征之间的关系。应用多因素回归分析、Kaplan-Meier方法、Log-rank检验分析临床数据。结果：肺腺癌组织中钙敏感受体阳性表达率明显低于正常组织(P=0.003)。统计学相关分析表明，在肺腺癌标本中，钙敏感受体的表达与E钙粘蛋白正相关(P<0.001)。高表达钙敏感受体(P=0.034)及E钙粘蛋白(P=0.001)的肺腺癌患者有更长的总生存时间。多因素回归分析显示联合标志物是总生存的独立预测因子(HR=0.440，95% CI，0.249~0.779，P=0.005)。结论：这项研究表明钙敏感受体是肺腺癌新的预后标志物，同样表明钙敏感受体可能作为肺腺癌新的治疗靶点。