| Objective：By analysis the expressions of NK cell ligand MICA(majorhistocompatibility complex class Ⅰ chain-related protein A)contained solubleMICA in the epithelial ovarian cancer patients serum and membrane MICA inthe epithelial ovarian cancer tissue and the expression of the stimulatoryreceptor NKG2D on the natural killer cell，we try to find the relationshipbetween their expressions and the different patho cell differentiation degreesand histology and clinical stage. Explore the correlation of sMCIA, mMICAand the expression of NKG2D. We also try to investigate the role ofsMICA-NKG2D in tumor immunological escape and their clinicalsignificance.Methods：The serum，tissue and peripheral blood of55cases of epithelialcancer patients were selected, compared with30cases of epithelium ovarianbenign tumor and15cases of uterine myoma.The serum levels of sMICA wereassessed by MICA-specific enzyme-linked immunosorbent assay.Immno-histochemisty ElivisionTMplus two-step was used to detect the distribution ofmMICA in epithelial ovarian tissues.NK cell was identified by three labeledantibodys and peripheral blood samples were collected to detect NKG2D byflow cytometry analysis. To use SPSS13.0statistical analysis softwareanalyze experimental data.p<0.05indicates that the difference had a statisticalsignificance.Results:1ELISA:the serum levels of sMICA(ng/ml)1.1The serum levels of sMICA were (22.98±6.58),(10.92±3.05) and(3.68±1.87) in55cases of epithelial ovarian cancer,30cases of epithelialovarian benign tumor and15cases of uterine myoma respectively.Comparedwith the benign tumor group and normal group, the serum levels of sMICA were highest in epithelial ovarian cancer. The difference had a statisticalsignificance(t=5.134,p=0.002;t=15.80, p=0.000,p<0.05).1.2The serum levels of sMICA of epithelial ovarian cancer were (27.07±4.32)and (16.52±4.11) in35cases of the poorly differentiaed patients and in20cases of the higher/moderately differentiated patients respectively.There wassignificant difference between the two groups, and the difference had astatistical significance(t=8.858,p=0.030，p<0.05).1.3The serum levels of sMICA of epithelial ovarian cancer were (14.43±2.51)and (25.49±5.16) in12cases of stage Ⅰ~Ⅱ and in43cases of stage Ⅲ~Ⅳrespectively.There were significant differences between the two groups, andthe difference had a statistical significance(t=10.794,p=0.017，p<0.05).1.4The serum levels of sMICA in different histological type of epithelialovarian cancer were22cases of endometrioid cancer（21.93±6.67）ng/ml,15cases of serous cancer（23.08±6.59）ng/ml,10cases of poorly differentiatedcarcinoma（25.73±7.11）ng/ml,8cases of mucinous cancer（22.78±5.64）ng/ml.Compared with each other, there were no obvious difference in differenthistological type of epithelial ovarian cancer (F=0.764,P=0.520，P<0.05).2Immunohistochemical ElivisionTMplus two-step:2.1There were35cases of positive expression of mMICA in55casesepithelial ovarian cancer tissues.The positive expression rate of mMICA was63.64%.In the30cases of benign oarian epithelial,2cases expression ofmMICA was positive.The positive expression rate of mMICA was6.67%.There was no expression in the15cases of normal oarian epithelial.The different positive expression of mMICA between the ovarian cancer groupand benign oarian tumor group, between the ovarian cancer group and thenormal group had a statistical significance（Χ2=37.392，P=0.000,P＜0.05）.2.2The positive expressions of mMICA were detected in18of35poorlydifferentiated epithelial ovarian cancers,17of20high/moderately differentiat-ed epithelial ovarian cancers respectively.And their positive expression ratesof mMICA were51.43%and85%. The statistical differences were foundbetween the two groups(Χ2=4.636,P=0.046,P<0.05). 2.3The positive expressions of mMICA were detected in11of12stageⅠ～Ⅱ epithelial ovarian cancers,24of37stageⅢ～Ⅳepithelial ovarian cancersrespectively.The expression rate of mMICA in stageⅠ～Ⅱ was higher thanthat in stageⅢ～Ⅳ,There were91.67%and55.81%respectively.The differe-nce had a statistical significance(Χ2=6.191,P=0.039,P＜0.05).2.4The strong positive expressions of mMICA in different histological type ofepithelial ovarian malignant tumor:14of22cases of endometrioidcarcinoma(the positive expression rate:63.64%),10of15cases of serouscarcinoma(the positive expression rate:66.67%),5of8cases of mucinouscarcinoma(the positive expression rate:62.5%),6of10cases of poorlydifferentiated carcinoma(the positive expression rate:60%).There were noobvious difference in different histological type of epithelial ovarianmalignant tumor(P=0.989,P>0.05).3Flow cytometrythe expression of NKG2D(‰)3.1The expression of NKG2D were(3.8628±1.8044),(21.0901±6.7900) and(38.9403±8.9249)in55cases of epithelial ovarian cancer,30cases of epithelialovarian benign tumor and15cases of normal group respectively.Comparedwith the epithelial ovarian benign tumor and the normal group,the expressionof NKG2D was lowest in epithelial ovarian cancer. The difference had astatistical significance(t=11.198, P=0.000; t=17.875, P=0.000).3.2The expression of NKG2D of epithelial ovarian cancer were(2.7348±0.9914) and (5.5161±1.4384) in35cases of the poorly differentiaedpatients and in20cases of the higher/moderately differentiated respective-ly.Compared with each other, the expression of NKG2D in the poorly differe-ntiated patients was the significantly lower. The difference had a statisticalsignificance (t=8.471,P=0.000,p<0.05).3.3The expression of NKG2D of epithelial ovarian cancer were (6.4615±1.1530) and (3.0853±1.1695) in12cases of stage Ⅰ~Ⅱ and in43cases ofstage Ⅲ~Ⅳ respectively.There were significant differences between the twogroups, and the difference had a statistical significance (t=7.313, P=0.008, p<0.05).3.4The expression of NKG2D of22cases of endometrioid cancer was(4.1526±1.9648),15cases of serous cancer(3.8631±1.8508),8cases of mucino-us cancer(3.7773±1.5185),10cases of poorly differentiated carcinoma (3.3109±1.4625).Compared with each other, there was no obvious difference indifferent histological type of epithelial ovarian cancer(F=0.512,P=0.676,P<0.05).4The correlation between the serum levels of sMICA and the expression ofNKG2D in peripheral blood in epithelial ovarian cancer patients：4.1The pearson correlation coefficient between the serum levels of sMICAand the expression of NKG2D in12cases of stage Ⅰ~Ⅱ was-0.832.Theywere present a negative correlation and had a statistical significance(p=0.002,P<0.05).4.2The pearson correlation coefficient between the serum levels of sMICAand the expression of NKG2D in43cases of stage Ⅲ~Ⅳ was-0.842.Theywere present a negative correlation and had a statistical significance(p=0.000,P<0.05).4.3The pearson correlation coefficient between the serum levels of sMICAand the expression of NKG2D in35cases of the poorly differentiaed patientswas-0.981.They were present a negative correlation and had a statisticalsignificance(p=0.000,P<0.05).4.4The pearson correlation coefficient between the serum levels of sMICAand the expression of NKG2D in20cases of the higher/moderately differen-tiated patients was-0.657.They were present a negative correlation and had astatistical significance(p=0.002,P<0.05).4.5The correlation between the serum levels of sMICA and the expression ofNKG2D in the endometrioid cancer of different histological types:In the endometrioid cancer r=-0.093,p=0.680; in the serous cancer r=-0.121,p=0.668;in mucinous cancer r=-0.142,p=0.738;in poorly differentiated r=-0.384,p=0.273.None of them had correlation(p=0.273，P>0.05). 5The correlation between the positive expression rate in certain group cancertissue which score three points and the serum levels of sMICA:5.1The spearman correlation coefficient between the positive cells expressionrate in35cases of the ovarian cancer tissues and the serum levels of sMICAwas-0.668.They were present a negative correlation and had a statisticalsignificance(P=0.000,P<0.05).5.2The Spearman correlation coefficient between the positive cells expressionrate in18cases of the poorly differentiated ovarian cancer tissues and theserum levels of sMICA-0.752,they were present a negative correlation andhad a statistical significance(P=0.000,P<0.05).5.3The Spearman correlation coefficient between the positive cells expressionrate in17cases of highly/moderately differentiated ovarian cancer tissues andthe serum levels of sMICA was-0.875.They were present a negative correla-tion and had a statistical significance(P=0.000,P<0.05).5.4The Spearman correlation coefficient between the positive cells expressionrate in11cases of stageⅠ～Ⅱcancer tissues and the serum levels of sMICA-0.506,P=0.078.They did not present a negative correlation and didn,t have astatistical significance(P=0.078,P<0.05).5.5The Spearman correlation coefficient between the positive cells expressionrate in24cases of stage Ⅲ～Ⅳ cancer tissues and the serum levels of sMICAin corresponding patients was-0.867.They were present a negative correlationand had a statistical significance(P=0.000,P<0.05).5.6There was no linear correlation in different histological type of epithelialovarian cancer tissues with the serum levels of sMICA in correspondingpatients.The correlation coefficient and p value were：in14cases of positiveendometrioid cancer the spearman correlation coefficient rs=-0.108,P=0.613;in10cases of positive serous cancer,rs=-0.366,P=0.219;in5cases ofpositive mucinous cancer the spearman correlation coefficient rs=-0.494,P=0.447;in6cases of positive poorly differentiated carcinoma, rs=-0.600,P=0.353.Conclusions:The serum levels of sMICA,the positive expression rate ofmMICA and the expression of NKG2D in epithelial ovarian cancer patients were correlated with the degree of differentiation of cancer cells and clinicalstage of the epithelial ovarian cancer.There was no correlation in differenthistological type of epithelial ovarian cancer tissues.The later clinical stageand higher pathological grade, the higher level of sMICA but the lowerpositive expression rate of mMICA and the lower expression of NKG2D.Theexpression of NKG2D and the positive expression rate of mMICA in epithelialovarian cancer were significantly decreased,but the serum levels of sMICAwas significantly escalated. All of them may be contribute to the progressionof ovarian cancer. NKG2D-sMICA may play a critical role in tumorimmunological escape in epithelial ocarian cancer. |
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