Objective To investigate the application value of FasL,Caspase-8 protein expression and Caspase-8 gene methylation in non-small cell lung cancer(NSCLC). Methods Totally 100 patients with NSCLC were selected,whose cancer tissues and paracancerous tissues(with tumor as the center of radius of 6 cm) were resected,among them;55 cases of pulmonary squamous cell carcinoma,30 cases of lung adenocarcinoma,and 15 cases of squamous cell carcinoma of the lung;50 cases were poorly differentiated carcinoma,30 cases were moderately differentiated carcinoma and 20 cases were highly differentiated carcinoma;there were 65 cases with lymph node metastasis,35 cases without lymph node metastasis,and 100 cases of normal lung tissue were taken as control. Immunohistochemical staining of S-P was used to detect the expression of FasL and Caspase-8 proteins in NSCLC specimens,methylation status of Cas-pase-8 gene in patients with NSCLC was detected by methylation specific polymerase chain reaction(PCR). Results FasL protein was mainly distributed in the serous layer of tumor cells,and a few were spread over the cell membrane. Caspase-8 protein distributed in the cell serous. In NSCLC,FasL protein and Caspase-8 protein in different degree of positive expression,the positive expression rate of FasL protein was significantly higher than those of adjacent tissues and normal tissues(P < 0. 05),the positive expression in lung adenocarcinoma was significantly higher than those in squamous cell carcinoma and squamous cell carcinoma(P < 0. 05),the positive expression rate in poorly differentiated carcinomas was obviously higher than those in moderately differentiated carcinoma and highly dif-ferentiated carcinoma(P < 0. 05),the positive rate of FasL protein in lymph node metastasis was significantly lower than that in non-lymphatic metastasis(P < 0. 05). The positive expression rate of Caspase-8 protein was significantly lower than those of adjacent tis-sues and normal tissues(P < 0. 05),the positive expression in lung adenocarcinoma was significantly lower than those in squamous cell carcinoma and squamous cell carcinoma(P < 0. 05),the positive expression rate in highly differentiated carcinomas was obviously higher than those in moderately differentiated carcinoma and poorly differentiated carcinoma(P < 0. 05),the positive rate of Caspase-8 protein in lymph node metastasis was significantly lower than that in non-lymphatic metastasis(P < 0. 05). The rate of Caspase-8 gene methylation in cancer tissues was significantly higher than that in adjacent tissues and normal tissues,the positive expression in lung adenocarcinoma was significantly higher than in squamous cell carcinoma and squamous cell carcinoma, the positive expression rate in poorly differentiated carcinomas is obviously higher than that of moderately differentiated carcinoma and highly differentiated carcinoma, the positive rate of Caspase-8 gene methylation in lymph node metastasis was significantly lower than that in non-lymphatic metasta-sis ( P < 0. 05 ) . Conclusion High expression of FasL protein and Caspase-8 gene hypermethylation in NSCLC can accelerate the rate of lung cancer cells and tumor cells in the joint,inhibit the activity of immune cells,result in tumor formation without immune region and promote tumor cell division and growth,which become an important cause of early metastasis of adenocarcinoma. The expression of Caspase-8 protein in squamous cell carcinoma is higher,which is the main prognostic factor of squamous cell carcinoma. It is also one of the important indexes to judge the prognosis of NSCLC. Caspase-8 is involved in the evolution of NSCLC,and is closely related to the occurrence,development and metastasis of NSCLC. As an important prognostic factor of NSCLC,Caspase-8 provides an important theoretical basis for the comprehensive and targeted treatment of NSCLC.%目的 探讨FasL和Caspase-8蛋白表达及Caspase-8基因甲基化在非小细胞肺癌中的应用价值.方法 选取手术切除的非小细胞肺癌患者100例,均分别切除癌组织和癌旁组织(以肿瘤为中心6 cm为半径的肺组织),其中肺鳞癌55例,肺腺癌30例,肺腺鳞癌15例;低分化癌50例,中分化癌30例,高分化癌20例;伴有淋巴转移65例,无淋巴转移35例.另取正常肺内组织100例进行对照.采用免疫组化S-P染色法检测非小细胞肺癌标本FasL和Caspase-8蛋白表达;采用甲基化特异性聚合酶链式反应检测非小细胞肺癌组患者的Caspase-8基因甲基化状态.结果 FasL蛋白主要散布在肿瘤细胞浆液中,少数排列在细胞膜上;Caspase-8蛋白散布于细胞浆液中.在非小细胞肺癌中,FasL蛋白及Caspase-8蛋白存在不同程度的阳性表达,FasL蛋白阳性表达率明显大于癌旁组织和正常组织,在肺腺癌的阳性表达率明显大于鳞癌及腺鳞癌(P<0.05),在低分化癌中的阳性表达率明显大于中分化癌及高分化癌,伴淋巴转移FasL蛋白阳性率大于非淋巴转移,差异均有统计学意义(P<0.05);而Caspase-8蛋白阳性表达率明显小于癌旁组织和正常组织,在肺腺癌的阳性表达率明显小于鳞癌及腺鳞癌,在高分化癌中的阳性表达率明显大于中分化癌及低分化癌,伴淋巴转移Caspase-8蛋白阳性率低于非淋巴转移,差异均有统计学意义(P<0.05).癌组织Caspase-8基因甲基化率明显大于癌旁组织和正常组织,在肺腺癌的阳性表达率明显大于在鳞癌及腺鳞癌的阳性表达率,在低分化癌中的阳性表达率明显大于中分化癌及高分化癌,伴淋巴转移Caspase-8基因甲基化阳性率高于非淋巴转移,差异均有统计学意义(P<0.05).结论 非小细胞肺癌中出现FasL蛋白高表达和Cas-pase-8基因高甲基化的变化,加快肺癌细胞与免疫细胞联合的速率,抑制免疫细胞的活性,致使肿瘤内部形成无免疫区域而促进肿瘤细胞的分裂和滋长,成为腺癌较易发生早期转移的重要原因.Caspase-8蛋白在鳞癌中表达增高,这是鳞癌预后较好的主要因素,也是判断非小细胞肺癌预后的重要指标之一.Caspase-8参与了非小细胞肺癌的演变,与非小细胞肺癌的发生、发展及转移有密切关系,作为非小细胞肺癌预后的重要指标,为临床对非小细胞肺癌进行综合性、针对性的治疗提供了重要理论依据.
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