The Expression Of FLIP And FAF1 In Gastric Carcinoma And The Relationship Between Immune Escape Of Fas/FasL And FLIP And FAF1

Objective:Gastric carcinoma is one of the most common tumor of the digestive system in the world.In China the incidence of gastric carcinoma is very high,and gastric carcinoma always threatens people,s heath badly.Consequently,it becomes a major reason of the difficulty of the cancer,s therapy that cancer cells escape the immune system watching and increase rapidly.It is a important mechanism of the development and the cancer,s difficult therapy of gastric carcinoma that the mechanism of Fas-induced apoptosis.Abnormality of Fas-inducing apoptosis in cancer cells is also a important mechanism of immune escape of tumor.Fas is a member of tumor necrosis factor receptor(TNFR)superfamily,and FasL is Fas ligand.Fas combines with FasL and induces cell apoptosis.In cell Fas death domain(DD) combines with the C terminal of Fas associated death domain,and the death effect domain(DED) of the N terminal of Fas associated death domain(FADD) interacts with caspase-8 and actives caspase-8.So apoptosis is beginning.Now the mechanism of the immune escape aboute Fas-induced apoptosis in cancer cell have two characters:firstly,the counterattack of Fas-inducing apoptosis,namely FasL of the cancer cells, surface counteract T cells, Fas and induce T cell apoptosis[1.2];secondly,the antagonism of Fas/FasL,in the cell level it is the obstacle of the mediation and control of the cell apoptotic signaling,including the increasing of inhibitor and the decreasing of promptor.c-FLIP is the one of the apoptotic inhibitor,and it has two DED which interacts with FADD and caspase-8.But it can not induce the apoptotic signaling and make the existence and development of the cancer cells which escape immune system watching.Fas-associated factor1 (FAF1) is a novel Fas-binding protein ,and it is associated with Fas.FAF1 doesn,t include DD,but the amino acids 181-381 region of FAF1 can interact with the DEDs of caspase-8 .This domain named DED-like domain(DEDID)[3].In the Fas-induced apoptosis,the function of FAF1 potentiates apoptosis.Because of immune system,the expression of FAF1 perhaps reduces in the cancer cells.In this study,we analyzed the expression of FLIP and FAF1 in gastric carcinoma,the relationship of FLIP and FAF1 and the relationship between FLIP,FAF1 and Fas,FasL.At the same time ,we want to know about the function of FLIP and FAF1 in the pathway of Fas-induced apotposis and offer the valuable theory for the biological therapy of inhibiting tumor immune.Methods:In this study,we used 38 patients, tissues which were cancer tissues,the brims of gastric carcinomas and the relatively normal tissues–the distanse between the normal to the cancer tissue about 5cm.The paraffin-embedded section of all the tissues was cut by surgical operation of the second hospital of HeBei Medical University.All the patients did not accept radio-therapy,chemical-therapy and hormone immunity therapy.The diagnosis of the pathology was explicit,and the clinical information was complete. 32 male and 6 femal,age 39～72 years old,median age is 55.5 years old.Pathology,stage and the condition of lymph node metastasis were appreciated by pathology Director.Control group had 10 examples for the normal mucous membrane of stomachs.We calculated the expression of Fas,FasL,FAF1 and FLIP with immnohistochemistry and the analysis of the semi-quantitative sort in the positive cells,and studied the relation between FAF1 and FLIP and the clinic pathology,s parameter of gastric carcinomas.Statistics handling used SPSS10.0 software.It used the Chi-Square test and Fisher exact probabilities for the comparision of the expression in every tisse and the relation between FAF1 and FLIP and the clinic pathology,s parameter of gastric carcinomas.It used the spearman test for the relation of Fas,FasL,FAF1 and FLIP.P < 0.05 is regard as having differences.Result:(1)Fas is expressed in 73.68% (28/38) of the gastric carcinomas.Fas is expressed in 84.21% (32/38) of the brim of gastric carcinomas.Fas is expressed in 97.37% (37/38) of the relative normal tissues.In this three tissues,the expression of Fas has distinct difference(P<0.05). FasL is expressed in 94.74% (36/38) of the gastric carcinomas.FasL is expressed in 86.84% (33/38) of the brim of gastric carcinomas.FasL is expressed in 68.42% (26/38) of the relative normal tissues.In this three tissues,the expression of FasL has distinct difference(P<0.05).(2) FAF1 is expressed in52.63% (20/38) of the gastric carcinomas.FAF1 is expressed in81.58% (31/38) of the brim of gastric carcinomas.FAF1 is expressed in86.84% (33/38) of the relative normal tissues.In this three tissues,the expression of FAF1 has distinct difference(P<0.05). FLIP is expressed in 92.11% (35/38) of the gastric carcinomas.FLIP is expressed in 78.95% (30/38) of the brim of gastric carcinomas.FasL is expressed in 55.26% (21/38) of the relative normal tissues.In this three tissues,the expression of FLIP has distinct difference(P<0.05).(3)The relation between FLIP and pathologicial parameter in the gastric carcinomas:the expression of FLIP in the different pathologicial parameter has not distinct difference(P>0.05).(4) The relation between FAF1 and pathologicial parameter in the gastric carcinomas:the expression of FAF1 in the different pathologicial parameter has not distinct difference except of the cancer diameter(P<0.05).(5)There is not correlation between FLIP and Fas or FAF1,as well FAF1 and Fas or FasL(P > 0.05).There is correlation between FLIP and FasL(P<0.05).Conclusion:(1)Fas is expressed in 73.68%(28/38) of the gastric carcinomas.Fas is expressed in 84.21%(32/38) of the brim of gastric carcinomas.Fas is expressed in 97.37%(37/38) of the relative normal tissues.In this three tissues,the expression of Fas has distinct difference(P<0.05). FasL is expressed in 94.74%(36/38) of the gastric carcinomas.FasL is expressed in 86.84%(33/38) of the brim of gastric carcinomas.FasL is expressed in 68.42%(26/38) of the relative normal tissues.In this three tissues,the expression of FasL has distinct difference(P<0.05).The study show the expression of Fas and FasL is abnormal in the cancer cells.Fas-induced apoptosis appears the counterattack in the gastric carcinomas.So this study shows the condition of the immune escape in the gastric carcinomas.(2) FAF1 is expressed in 52.63%(20/38) of the gastric carcinomas.FAF1 is expressed in81.58%(31/38) of the brim of gastric carcinomas.FAF1 is expressed in 86.84%(33/38) of the relative normal tissues.In this three tissues,the expression of FAF1 has distinct difference(P<0.05). FLIP is expressed in 92.11%(35/38) of the gastric carcinomas.FLIP is expressed in 78.95%(30/38) of the brim of gastric carcinomas.FasL is expressed in 55.26%(21/38) of the relative normal tissues.In this three tissues,the expression of FLIP has distinct difference(P<0.05),this study shows the high expression of FLIP in gastric carcinomas.The increase of FLIP and the decrease of FAF1 are two major factors of the recurrence and development of the gastric carcinomas.(3)The relation between FLIP and pathologicial parameter in the gastric carcinomas:the expression of FLIP in the different pathologicial parameter has not distinct difference(P>0.05).It shows FLIP is in no relation to the pathologicial parameter.(4) The relation between FAF1 and pathologicial parameter in the gastric carcinomas:the expression of FAF1 in the different pathologicial parameter has not distinct difference except of the cancer diameter(P<0.05). It shows FAF1 is in relation to the cancer diameter.(5)There is not correlation between FLIP and Fas or FAF1,as well FAF1 and Fas or FasL(P > 0.05).There is correlation between FLIP and FasL(P<0.05).It shows the relation between FLIP immune escape.