结直肠癌中LC3与CD4+、CD8+、CD68+免疫细胞浸润的相关性及其临床意义

摘要

目的 观察自噬标志物LC3与肿瘤表面抗原NY-ESO-2、MAGE-D4在结直肠癌及癌旁正常黏膜组织中的表达以及 CD4+、CD8+、CD68 +免疫细胞的浸润情况,分析LC3与NY-ESO-2、MAGE-D4以及CD4+、CD8+、CD68 +免疫细胞浸润的相关性,探讨结直肠癌细胞自噬对免疫细胞的影响及其临床意义.方法 应用免疫组化EnVision法、Western blot法检测128例结直肠癌及癌旁正常黏膜组织中LC3、NY-ESO-2、MAGE-D4的表达以及CD4+、CD8+、CD68+免疫细胞浸润情况,探讨各因子之间的相关性并结合临床病理特征进行分析.结果 (1)LC3在结直肠癌组织中的表达高于癌旁正常黏膜组织,NY-ESO-2在结直肠癌中低表达,MAGE-D4在结直肠癌中高表达,两者在癌旁正常黏膜组织中几乎不表达(P＜0.05) ;CD4+、CD8 +、CD68 +免疫细胞在结直肠癌中的浸润量均高于癌旁正常黏膜组(P＜0.05) ;(2)结直肠癌中LC3与肿瘤表面抗原NY-ES0-2、MAGE-D4的表达以及CD4 +、CD8 +、CD68 +细胞的浸润量均呈正相关(P＜0.05) ; (3) NY-ESO-2的表达与CD4 +、CD8 +、CD68 +细胞的浸润量均呈正相关,MAGE-D4的表达与CD8+、CD68 +细胞的浸润量均呈正相关(P＜0.05) ; (4) LC3、NY-ESO-2、MAGE-D4的表达及CD4+、CD8+免疫细胞的浸润量均与淋巴结转移呈负相关(P＜0.05);LC3、NY-ESO-2、MAGE-D4的表达及CD4+、 CD8+、CD68+细胞的浸润量与TNM分期呈负相关(P＜0.05) ;LC3的表达与结直肠癌的分化程度呈正相关;CD8+细胞的浸润量与组织学分级呈正相关(P＜0.05).结论 结直肠癌中自噬标志物LC3的表达与肿瘤表面抗原NY-ESO-2、MAGE-D4的表达、免疫细胞CD4+、CD8+、CD68 +的浸润量具有相关性,自噬活性改变可能影响结直肠癌的细胞免疫.%Purpose To observe the expressions of LC3, NY-ES0-2, MAGE-D4, CD4+, CD8+, CD68+ in colorectal cancer and normal tissues and analysis the correlation of autophagy related gene LC3 and tumor surface antigen NY-ES0-2, MAGE-D4, immune cells CD4+, CD8+, CD68 +. To investigate the effect of the change of autophagy on immune cells function and its clinical significance. Methods Immunohistochemistry and Western blot were used to detect the expressions of LC3, NY-ESO-2, MAGE-D4, CD4, CD8, CD68 in 128 cases of colorectal cancer and normal tissues. The correlation among each factors and the patients' clinicopathological features were analyzed. Results (1 ) The expression of LC3 in colorectal cancer tissue was higher than in normal tissues. The expression of NY-ESO-2 was low while the expression of MAGE-D4 was high in colorectal cancer and both almost not express in normal tissues(P＜0.05). The infiltration of CD4+, CD8 +, CD68+ immune cells in colorectal cancer were higher than in normal tissues(P＜0.05). (2)The expression of LC3 protein in colorectal cancer was correlated positively with the expressions of tumor surface antigen NY-ESO-2, MAGE-D4 protein and the infiltration of CD8 +, CD68 + immune cells (P＜ 0.05 ), but had no correlation with the infiltration of CD4 + immune cells (P＞0.05). (3 ) The expression of NY-ESO-2 was correlated positively with the infiltration of CD4+, CD8 +, CD68 + immune cells. The expression of MAGE-D4 was correlated positively with the infiltration of CD8 +, CD68+ immune cells. (4) The expressions of NY-ESO-2, MAGE-D4, the infiltration of CD4+, CD8 + immune cells and lymph node metastasis were negatively correlated (P＜0.05). The expressions of NY-ESO-2, MAGE-D4, the infiltration of CD4+, CD8+ immune cells and TNM stage were negatively correlated (P＜ 0.05). The infiltration of CD8 + immune cells and grade was positively correlated (P＜0.05). Conclusion The expression of autophagy-related gene LC3 was related to the expressions of tumor surface antigen NY-ESO-2, MAGE-D4 and the infiltration of immune cells CD8 + and CD68+ in colorectal cancer. Therefore the autophagy key factor LC3 may participate in the immune of colorectal cancer.