gp96与免疫相关基因CTLA-4、CD8在肺癌组织芯片中的表达及意义

BACKGROUND AND OBJECTIVE: It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. METHODS: We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. RESULTS: (1) The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05). The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05). The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05). The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05). (2) The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05), but not to age, gross type, histological type and lymph node metastasis (P > 0.05). The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05), but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05). CD8 expression was related to clinical stage (P < 0.05), but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05). The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3) There was positive correlation between gp96 and CTLA-4; there was negative correlation between gp96 and CD8, and there was negative correlation between CD8 and CTLA-4 (P < 0.05). CONCLUSION: Gene expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.