负性共刺激分子B7-H4在结直肠癌及其微环境中的表达及临床意义

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负性共刺激分子B7-H4是新近发现的B7家族的新成员。为了检测人结直肠癌组织中肿瘤细胞及肿瘤浸润淋巴细胞(tumor-infiltrating lymphocyte,TIL)上B7-H4的表达以及分析巨噬细胞、T淋巴细胞及其亚群的浸润,进而探讨其相关临床意义,本课题采用免疫组化SP法检测98例人结直肠癌组织中肿瘤细胞及浸润淋巴细胞上B7-H4的表达以及巨噬细胞、T细胞及其亚群的浸润,统计学分析B7-H4的表达与患者临床病理参数、预后、肿瘤相关巨噬细胞(tumor-associated mac-rophage,TAM)以及CD3+T细胞、CD8+T细胞浸润程度的相关性。结果显示,结直肠癌组织中高表达B7-H4分子,而正常组织中基本不表达,并且在肿瘤细胞及浸润淋巴细胞中均检测到B7-H4的表达。统计学分析表明,浸润淋巴细胞中B7-H4的表达与患者年龄、有无淋巴结转移、是否为粘液腺癌有关(P<0.05),与患者总体生存率呈负相关(P<0.05),且B7-H4高表达组织较B7-H4低表达组织CD3+T细胞高度浸润例数显著增加(P<0.05);肠癌细胞中B7-H4的表达与患者肿瘤分期、淋巴结转移、有无远处转移以及Dukes分期有关(P<0.05)。综上所述,人结直肠癌患者的肠癌细胞及浸润淋巴细胞较正常细胞均异常表达B7-H4分子,CD3+T细胞的浸润程度与浸润淋巴细胞中B7-H4的表达呈显著相关而与肿瘤细胞上B7-H4的表达无关,而肿瘤细胞表达B7-H4与肿瘤分期、淋巴结转移、有无远处转移以及Dukes分期有关。上述结果提示肿瘤细胞表达B7-H4与浸润淋巴细胞表达B7-H4可能分别以不同机制参与了肿瘤的发生和进展,进一步分析肿瘤组织中B7-H4在不同细胞表达的生物学和临床意义具有重要的价值。 Negative costimulatory molecule B7-H4 is a newly discovered member of the B7 family. In order to detect the expression of B7-H4 on tumor cells and tumor-infiltrating lymphocytes (TILs) in human colorectal cancer tissues and to analyze the infiltration of macrophages, T lymphocytes and their subpopulations, In this study, immunohistochemical SP method was used to detect the expression of B7-H4 and the infiltration of macrophages, T cells and their subsets on tumor cells and infiltrating lymphocytes in 98 human colorectal cancer tissues. Statistical analysis of B7- H4 expression and clinicopathological parameters, prognosis, tumor-associated macrophage (TAM) and CD3 T cells, CD8 T cell infiltration degree correlation. The results showed that B7-H4 molecules were highly expressed in colorectal cancer tissues but not in normal tissues, and the expression of B7-H4 was detected in tumor cells and infiltrating lymphocytes. Statistical analysis showed that the expression of B7-H4 in infiltrating lymphocytes was correlated with age, lymph node metastasis and mucinous adenocarcinoma (P <0.05), but negatively correlated with overall survival (P <0.05), and The number of highly infiltrated CD3 + T cells in B7-H4 overexpression tissues was significantly higher than that in B7-H4 low expressive tissues (P <0.05). The expression of B7-H4 in colorectal cancer cells was significantly correlated with tumor stage, lymph node metastasis, Metastasis and Duke’s staging (P <0.05). In conclusion, B7-H4 molecules are abnormally expressed in colorectal cancer cells and infiltrating lymphocytes in normal colorectal cancer patients, and the infiltration of CD3 + T cells is significantly correlated with the expression of B7-H4 in infiltrating lymphocytes It was not related to the expression of B7-H4 in tumor cells. However, the expression of B7-H4 in tumor cells was related to tumor stage, lymph node metastasis, distant metastasis and Duke’s staging. The above results suggest that the expression of B7-H4 in tumor cells and infiltrating lymphocytes may be involved in the occurrence and progression of tumors by different mechanisms respectively. It is important to further analyze the biological and clinical significance of B7-H4 in different cell types in tumor tissues the value of.
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