HHLA2在口腔鳞状细胞癌免疫炎症微环境的表达及临床意义

发布时间：2018-03-20 02:22

本文选题：口腔鳞状细胞癌　切入点：HHLA2　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:口腔鳞状细胞癌的发生发展是人体内多种因素相互作用的复杂的病理过程,其中免疫炎症微环境的改变是重要的环节,并且免疫炎症微环境变化贯穿于发生发展过程的始终,即由黏膜到异常增生再到原位癌。HHLA2(B7H7/B7-H5)是最新发现的B7家族的成员,在许多正常组织中不表达,而在肿瘤中呈现高表达,并且表现与肿瘤的淋巴结转移有一定相关性。本文通过免疫组化研究并分析HHLA2及体内相关免疫炎症指标的变化,分析相互间相关性,探讨其在OSCC发生发展过程中的可能作用机制,评测其作为病理诊断的辅助诊断的应用价值。研究方法:选取41例口腔鳞状细胞癌、8例异常增生和9例正常口腔黏膜组织,借助组织微阵列免疫组织化学技术分析口腔正常黏膜组织,口腔异常增生组及口腔鳞状细胞癌中HHLA-2,PD-L1,PD-L2,细胞因子Il-6,M2型巨噬细胞标记物(CD163,CD206),T细胞(CD4,CD8),EGFR蛋白的表达情况,从而探讨其在口腔异常增生及口腔鳞状细胞癌中的相关性及其表达意义,进一步明确其在口腔鳞状细胞癌发病机制的影响,为口腔鳞状细胞癌的早期诊断提供参考。结果:(1)HHLA-2,IL-6在正常黏膜、口腔异常增生,口腔鳞状细胞癌中表达率依次增高,而正常黏膜和口腔鳞状细胞癌组间阳性率具有统计学差异(P0.05),且淋巴结转移组相对于未转移组表达率差异有明显统计学差异(P0.05)。(2)PD-L1,CD206和CD8在正常黏膜、口腔异常增生,口腔鳞状细胞癌中表达率依次增高,但表达率并不具有统计学意义。PD-L2,CD-4,CD206在正常黏膜、口腔异常增生,口腔鳞状细胞癌中表达率依次增高,口腔异常增生和口腔鳞状细胞癌相对于正常黏膜,表达量具有统计学差异(P0.05)。(3)EGFR在口腔鳞状细胞癌中表达量相对于正常黏膜,表达量具有统计学差异(P0.05)。CD163,CD4在正常黏膜、口腔异常增生,口腔鳞状细胞癌中表达率依次增高,口腔异常增生和口腔鳞状细胞癌相对于正常黏膜,表达量具有统计学差异(P0.05),且淋巴结转移组相对于未转移组表达率差异有明显统计学差异(P0.05)。(4)HHLA-2的表达量与PD-L1,PD-L2,M2巨噬细胞(CD163,CD206),IL-6的表达呈正相关。(5)PD-L1,PD-L2分别与EGFR正相关,而EGFR与CD4,CD8负相关。结论:HHLA-2,M2型巨噬细胞与PD-L1.PD-L2在口腔鳞状细胞癌的发生发展中起着一定作用。HHLA-2、PD-L1、PD-L2具有抑制CD4,CD8细胞增殖作用,可能由于抑制了EGFR受体。HHLA-2与PD-L1,PD-L2,M2型巨噬细胞表达呈正相关,可能在口腔黏膜发展到口腔癌这一过程中具有协同作用.
[Abstract]:Objective: the occurrence and development of oral squamous cell carcinoma (OSCC) is a complicated pathological process of interaction of many factors in human body, in which the change of immune inflammation microenvironment is an important link. And the changes of immune inflammation microenvironment throughout the process of occurrence and development, that is, from mucous membrane to abnormal proliferation to cancer in situ. H2HLA-B7H7 / B7-H) is a member of the newly discovered B7 family, which is not expressed in many normal tissues, but is highly expressed in tumors. The expression was correlated with lymph node metastasis. The changes of HHLA2 and related immune inflammation indexes in vivo were analyzed by immunohistochemistry, and the correlation between them was analyzed. To explore the possible mechanism of OSCC and evaluate its application value as auxiliary diagnosis of pathological diagnosis. Methods: 41 cases of oral squamous cell carcinoma (OSCC) with abnormal hyperplasia and 9 cases of normal oral mucosal tissue were selected. The expression of HHLA-2PD-L1pPD-L1 PD-L2 and the cytokine Il-6M2-type macrophage marker, CD163C / CD206 ~ (+) T cell, in normal oral mucosa, dysplasia of oral cavity and oral squamous cell carcinoma (OSCC) were analyzed by microarray immunohistochemical technique, and the expression of CD4 / CD8EGFR protein was detected in normal oral mucosa, dysplasia of oral cavity and oral squamous cell carcinoma (OSCC). To explore the correlation and significance of its expression in oral dysplasia and oral squamous cell carcinoma (OSCC), and to further clarify its role in the pathogenesis of oral squamous cell carcinoma (OSCC). Results in normal mucosa, abnormal proliferation of oral cavity and oral squamous cell carcinoma, the expression rate of HHLA-2C6 in oral squamous cell carcinoma increased in turn. The positive rates of CD206 and CD8 in normal mucosa and oral squamous cell carcinoma group were significantly different compared with those in non-metastasis group (P 0.05), and the expression of CD206 and CD8 in normal mucosa and oral cavity were abnormal in lymph node metastasis group. In oral squamous cell carcinoma, the expression rate increased in turn, but the expression rate was not statistically significant in normal mucosa, oral dysplasia, oral squamous cell carcinoma and oral squamous cell carcinoma. Compared with the normal mucosa, the expression of P0.05U. 3EGFR in oral squamous cell carcinoma and oral squamous cell carcinoma was significantly different from that in normal mucosa. The expression level of P0.05 + CD163T CD4 in normal mucosa was significantly different from that in normal mucosa, and the expression of CD163T CD4 in oral squamous cell carcinoma was significantly higher than that in normal mucosa, and the expression of CD163T CD4 in oral squamous cell carcinoma was significantly higher than that in oral squamous cell carcinoma. The expression rate of oral squamous cell carcinoma (OSCC) increased in turn, and the abnormal proliferation of oral cavity and oral squamous cell carcinoma (OSCC) were relative to normal mucosa. The expression of HHLA-2 in lymph node metastasis group was significantly different from that in non-metastasis group. The expression of HHLA-2 in lymph node metastasis group was positively correlated with the expression of EGFR in macrophages of PD-L1 and PD-L2M2.The expression of IL-6 was positively correlated with the expression of CD163mCD206, and the expression of PD-L1PD-L2 was positively correlated with the expression of EGFR in the lymph node metastasis group, and the positive correlation was found between the expression of HHLA-2 in the lymph node metastasis group and that in the macrophage of PD-L1 and PD-L2m-2 macrophages. Conclusion EGFR and PD-L1.PD-L2 play a role in the development of oral squamous cell carcinoma. HHLA-2pPD-L1PD-L2 can inhibit the proliferation of CD4 / CD8 cells, which may be due to the inhibition of the expression of EGFR receptor. HHLA-2 and PD-L1 / M 2 macrophages are positively correlated with the expression of PD-L1PD-L2 type M 2 macrophages. May have a synergistic effect in the development of oral mucosa to oral cancer.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.8

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