| Background and objective:Malignant tumor development or degeneration,to some extent,is dependent upon the interaction between the tumor and the host immunity system. Malignant tumors have been able to unrestricted growth, high incidence of distant metastasis, in addition to its own characteristics and, more importantly closely related with the tumor cells to escape host immune surveillance.It is found that there are two message pathways to regulate cell apoptosis:mitochondria C pathway and death receptor pathway.FasL is an important apoptosis molecule,which can couple with its death receptor Fas to induce apoptosis of Fas positive cells. Now some studies have found that many kinds of malignant cells were found FasL protein overexpression facilitates tumor cells killing activated immune cells surrounding them. Abnormal expression of Fas working in coordination with over expressed FasL lead to immune evasion through escaping immunosurvellance.Caspase is the main enzymes to execute apoptosis,and caspase-8plays an important role as a promoter in a cascade of caspase enzymes.And some studies have found that DNA methylation mechanisms are involved in tumorigenesis Methylation of the promoter regions of CpG-rich sites in Caspase-8,an apoptosis inducing cysteine protease is the major mechanism for the sileneing of this gene in tumors,and may contribute to an inereased mutation and allelic loss of this gcne.Expression of the Caspase-8gene is reduced or absent in many human cancers,such as neuroblastoma,head and neck carcinoma,uterine cervix caneer,carcinoma of bladder,colorectal cancer,gastric cancer and esophagus squamous carcinoma,et al.However,to our knowledge,little is known regarding expression,role and the methylation of Caspase-8in lung carcinoma. In this study, through observation of human non-small cell lung cancer of different organizations, different types of metastatic lymph nodes of FasL protein expression of caspase-8and caspase-8gene methylation status. Study on the correlation of FasL and caspase-8protein protein expression and caspase-8gene methylation status.Investigate FasL and caspase-8protein expression and caspase-8gene methylation status in non-small cell lung cancer and its clinical significance in the development occurs.In order to provides a powerful way and reliable basis for the comprehensive treatment of non-small cell lung cancer.Experimental data and methods:1. This experiment to collect the First Affiliated Hospital of Suzhou University of thoracic surgery in March2010to March2011treatment surgical resection of non-small cell lung cancer and adjacent tissues (less than5cm from the tumor lung tissue) of80cases.56cases of male patients,24cases of female patients, age40to78years, the average age of58.6±10.56years.And45cases of lung squamous cell carcinoma,24cases of lung adenocarcinoma and11cases of lung adenosquamous carcinoma.Poorly differentiated carcinoma in38cases, moderately differentiated carcinoma in25cases,17cases of well-differentiated carcinoma. Clinical stage:according to the1997International Union Against Cancer (UICC) TNM staging standard,16cases in stage Ⅰ,Ⅱ of29cases,35cases is stage Ⅲ.With regional lymph node metastasis is46cases,34cases of non-regional lymph node metastasis. At the same time take the normal lung tissue specimens of52cases as controls (away from the tumor tissue5cm away).2. Use S-P immunohistochemical staining method to detect non-small cell lung cancer patients with FasL, Caspase-8protein expression.3. Modified by the sub-sulfated and methylation-specific polymerase chain reaction, MS-PCR to detection Caspase-8gene methylation status of non-small cell lung cancer patients.4. Statistical analysis was performed by using the software SPSS13.0.The experimental results:1. The results of FasL expression in non-small cell lung cancer:There are varying degrees of positive expression of FasL in80cases of tumor specimens, FasL protein is mainly distributed in the cytoplasm of tumor cells, a small part in the cell membrane surface, the positive expression rate was significantly higher than the adjacent tissues positive expression rate and normal tissues of the positive expression rate,P<0.05;FasL positive expression in lung adenocarcinoma percentage is significantly higher than the positive expression rates in squamous cell carcinoma, and adenosquamous carcinoma of the positive expression rate,P<0.05;FasL protein exprese in the metastasis to the lymph is higher than non-transfer of lymph node positive rate,P<0.05;FasL protein expression in different TNM stages of lung cancer difference was not significant(P>0.05).Moreover, the relationship between non-small cell lung cancer and tumor location,age and sex are found no significant difference among the groups, no statistically significant (P>0.05).2. The results of Caspase-8expression in non-small cell lung cancer:The distribution of caspase-8protein is in the cytoplasm,the positive expression rate is significantly lower than the cancer next to the organization a positive rate and normal tissue positive rate,P<0.01;and the expression in lung adenocarcinoma positive rate is significantly lower than the lung squamous cell carcinoma of the positive rate and adenosquamous carcinoma of the positive rate(P<0.05);the caspase-8protein expression in well-differentiated carcinoma positive rate is higher than middle and poorly differentiated carcinoma,there were significant differences(P<0.05);Caspase-8protein expression in metastatic lymph group is lower than non-metastatic lymph node group,the difference was statistically significant(P<0.05);Similarly,the caspase-8protein express in non-small cell lung cancer was no significant in different TNM stage,tumor location, age and gender expression(P>0.05).3. The results of Caspase-8gene methylation expression in non-small cell lung cancer:In the cancer tissue,caspase-8gene methylation is significantly higher than the adjacent tissues and normal lung tissue,P<0.01;In lung adenocarcinoma caspase-8gene methylation of the expression level is significantly higher than lung squamous cell carcinoma and adenosquamous carcinoma,P<0.05;In the metastasis to lymph nodes,caspase-8gene methylation-positive rate is higher than non-metastatic lymph node-positive rate,between the two groups,P<0.05;and the expression of caspase-8gene methylation in various degrees of differentiation and TNM staging of lung cancer and no significant differences between age and sex and tumor location were no significant difference,not statistically significant (P>0.05). 4. The results of the caspase-8gene methylation status and the caspase-8protein expression in non-small cell lung cancer:There were43cases of caspase-8gene methylation-positive expressed in non-small cell lung cancer,11cases of caspase-8protein expression were positive;37cases of negative expression of caspase-8gene methylation in lung cancer patients,19cases of caspase-8protein expression was negative.Use the x2correlation analysis test,caspase-8gene methylation and caspase-8protein expression was negatively correlated(r=-0.239,P<0.05).Conclusion:1. There was FasL protein expression increased significantly and caspase-8gene hypermethylation performance in non-small cell lung cancer.Use that Lung cancer cells can make to help tumor cells to anti-anti-immune activity of cells, so that the local tumor and was conducive to tumor development and metastasis formation of an immune amnesty parts; and this was may become an important reason for adenocarcinoma are more prone to early metastasis.2. Significant caspase-8protein expression decreased in non-small cell lung cancer,and increased expression of caspase-8in squamous cell carcinoma,which was become a good reason for squamous cell carcinoma prognosis than adenocarcinoma; and may become an important indicator to judge the prognosis of non-small cell lung cancer.3. Caspase-8protein expression lower was negatively correlated with its gene to the promoter region of5’-CpG island hypermethylation in non-small cell lung cancer. |
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