The Expression Of HLA-G In Peripheral Blood And Gastric Cancer Tissues And Its Clinical Significance

Objectve: Gastric cancer is one of malignant digestive tumors in our country, and it harmed people′s health. There is no any significant break through in its treatment, although the gastric cancer has been adopted multi-method therapies and its survival rate has risen. The one cause of difficult to cure relates to tumor immune escape.Human leukocyte antigen-G (HLA-G) belongs to nonclassical HLA-I. It expresses at trophoblast of mother-fetus interface, and participate immune tolerance. In normal, it is an important factor which does not cause mother'rejection to fetus.It is necessary to the success of encyesis. Recently, researches have proved that HLA-G has relations with organ transplantations, reproductions, tumors, and so on. It is an important agent which causes immune tolerance.It can suppress lymphocyte CD4+T cells directly, induce apoptosis of CD8+T cells, suppress the cytolysis of NK cells, which can influence the immunity reaction.In this experiment we monitored the expression of HLA-G,T lymphocyte subgroup and NK cell activity in the patients with gastric cancer, to investigate the local and total immune status of gastric cancer patients and the effect of HLA-G in immune escape, reveal the possible mechanisms by which tumors escape from surveillance of the body and provide more theoretical evidence for the improvements of immunotherapy for tumors.Methods: HLA-G was an factor of related to immune escape, which derived from gastric cancer patients was assayed in cancer tissues, normal gastric mucosa and peripheral blood mononuclearcell, respectively, at the same time, detected the marks of T lymphocyte subgroup and NK cells in cancer tissues and peripheral blood from patients of gastric cancer with Flow Cytometry (FAC).Results:1 Distribution of T cell subgroup and NK cell in gastric cancer and peripheral bloodThe ratio of CD3+,CD4+,CD8+,CD4+/CD8+ and NK cell in gastric cancer tissue were 33.90±9.78,37.44±8.90,36.40±8.86,0.51±0.11,9.28±3.37 respectively; the ratio of CD3+,CD4+,CD8+,CD4+/CD8+ and NK cell in peripheral blood were 58.90±10.85,52.01±9.55,20.66±5.19,1.57±0.49,19.94±6.28 respectively. Their ratio of CD3+,CD4+,CD4+/CD8+ and NK cell in gastric cancer were lower than them in peripheral blood respectively, the differences were statistically significant(p<0.05). The ratio of CD8+ T cell were higher in gastric cancer than it in peripheral blood, the differences were statistically significant (p<0.05).2 The expressions of HLA-G in gastric cancer, normal gastric mucosa and peripheral blood mononuclearcell The expression of HLA-G in gastric cancer, normal gastric mucosa and peripheral blood mononuclearcell were 1.24±0.25,0.94±0.31,1.00±0.22 respectively, the expression of HLA-G in cancer group was higher than that in normal gastric mucosa group(p<0.05)and peripheral blood group(p<0.05). There was no relation between normal gastric mucosa group and peripheral blood group.3 Correlations of the expressions of HLA-G and the T cell subgroup, NK cell in the cancer tissue and peripheral blood of gastric cancer3.1 Correlations of the expressions of HLA-G and the T cell subgroup, NK cell in the gastric cancer tissueThe expression of HLA-G in gastric cancer tissue was significantly and negatively correlated with the ratio of CD3+,CD4+,CD4+/CD8+ and NK cell(r=-0.580, r=-0.724, p<0.01)(r=-0.630, r=-0.422, p<0.05), but it was significantly and positively correlated with the ratio of CD8+ T cell(r=0.416, p<0.05).3.2 Correlations of the expressions of HLA-G and the T cell subgroup, NK cell in the peripheral blood of gastric cancer The peripheral expression of HLA-G was significantly and negatively correlated with the ratio of CD3+,CD4+,CD4+/CD8+ and NK cell(r=-0.570, r=-0.454, r=-0.560, r=-0.460, p<0.01), but it was significantly and positively correlated with the ratio of CD8+ T cell(r=0.312, p<0.05).4 Correlations of HLA-G expression in the gastric cancer tissue and clinicopathologic parameters of gastric cancer4.1 The expression of HLA-G in poorly differentiated adenocarcinoma group 1.35±0.24 was higher obviously than them in well and moderately differentiated group 1.03±0.19, the difference was statistically significant (p<0.01).4.2 The expression of HLA-G in lymphadens with and without metastasis was 1.36±0.13 and 0.99±0.25, the expression in metastasis group were higher than it in non-metastasis group respectively, the differences were statistically significant (p<0.01).4.3 The expressions of HLA-G in stageⅢ-ⅣandⅠ-Ⅱgroup were 1.30±0.28 and 1.07±0.22, Their expression in stageⅢ-Ⅳgroup was higher than them in stageⅠ-Ⅱgroup respectively, the differences were statistically significant(p<0.05).4.4 The expression of HLA-G hadn't relation with the age, gender, diameter of tumor, Borrmann type, depth of infiltration, and tumor embolus(p>0.05).Conclusions:1 The local T, NK cell immune function in gastric cancer patient is lower than that in peripheral blood. The rates of CD3+,CD4+,CD4+/CD8+ and NK cell in gastric cancer tissue are higher than those in the peripheral blood, but the rate of CD8+ T cell is higher. In gastric cancer, the local of T and NK cell immune function are low or suppressed.2 The expression of HLA-G in gastric cancer tissue and peripheral blood mononuclearcell is significantly and negatively correlated with CD3+,CD4+,CD4+/CD8+ and NK cell, and it is significantly and positively correlated with the CD8+ ratio activity, indicating that HLA-G is significantly correlated with the immune function.3 We detect the expression of HLA-G protein by Flow Cytometry in the gastric cancer, normal gastric mucosa and peripheral blood mononuclearcell, the expression of HLA-G in cancer group is higher than that in normal gastric mucosa group and peripheral blood group. The high expression of HLA-G in gastric cancer may be leading immune escape of gastric cancer.4 There are obviously relation between HLA-G and the differential degree, TNM stage and lymph node metastasis, indicating that the high expression of HLA-G bring out immune escape, accordingly, it maybe responsible for the carcinogenesis and development of gastric cancer.