Abstract:

Objective　To detect the expression levels of P16, TAP1, TAP2, HLA, and CD8 in laryngeal squamous cell carcinoma, and to explore the expression levels of TAP1, TAP2, HLA, and CD8 in laryngeal squamous cell carcinoma, and their correlations with HPV infection and the clinical significance. Methods　The tissue wax blocks from 84 patients with laryngeal squamous cell carcinoma surgically removed from Binzhou Medical University Hospital from January 2013 to December 2018 were selected as the study objects, including 68 males and 16 females; they were 45-78 years old, with a median age of 63. The expression levels of P16, TAP1, TAP2, HLA, and CD8 in the 84 cases of laryngeal squamous cell carcinoma was detected by the immunohistochemical EnVision method. The relationship between P16 and the clinicopathological features was analyzed. χ² test, Fisher exact test, and Spearman rank correlation test were used to analyze the correlation between HPV infection and the above protein expression levels. The Kaplan-Meier survival analysis was performed, and the Cox proportional risk regression model was used for the multivariate survival analysis. Results　The positive expression rate of P16 in laryngeal squamous cell carcinoma was 11.9% (10/84), while the expression was negative in the adjacent tissue. The positive rate of CD8 in laryngeal squamous cell carcinoma was 38.1% (32/84), which was lower than that in the adjacent tissue [56% (47/84)]. The positive rates of TAP1, TAP2, and HLA in the laryngeal squamous cell carcinoma tissue were 41.7% (35/84), 29.8% (25/84), and 42.8% (36/84), respectively, which were lower than those in the adjacent tissue [69% (58/84), 56% (47/84), and 57.1% (48/84)]; there was a statistical difference in the expression of TAP2 between the cancer and adjacent tissues (χ²=5.80, P<0.05). The expression of CD8 in the laryngeal squamous cell carcinoma tissue was correlated with clinical stage, and the difference was statistically significant (χ²=6.57, P<0.05). The expressions of TAP1, TAP2, HLA, and P16 were not correlated with the clinicopathological factors. The Spearman correlation analysis showed that the TAP1 expression was positively correlated with TAP2 and CD8 (r= 0.295 and 0.232, both P<0.05), and the HLA expression was positively correlated with the CD8 expression (r=0.232, P<0.05). Conclusion　The low expression levels of TAP1, TAP2, HLA, and CD8 in laryngeal squamous cell carcinoma tissue suggests that the tumor may down-regulate TAP1 and TAP2, resulting in abnormal HLA expression, thereby inhibits the immune response of CD8 and the immune response of the body, providing theoretical support for the mechanism of tumor immune escape.

Key words:

Laryngeal squamous cell carcinoma, TAP, HPV, Tumor immunity

摘要：

目的　检测抑制基因蛋白16（P16）与抗原加工相关转运体（TAP）1、TAP2、人类白细胞抗原（HLA）、CD8在喉鳞状细胞癌中的表达，探讨喉鳞状细胞癌中TAP1、TAP2、HLA、CD8的表达及其与人乳头瘤病毒（HPV）感染的相关性及临床意义。方法　选取滨州医学院附属医院2013年1月至2018年12月行手术切除的84例喉鳞状细胞癌患者的组织蜡块进行临床研究，其中男性68例，女性16例，年龄45～78岁，中位年龄63岁，采用免疫组化EnVision法检测84例喉鳞状细胞癌组织中P16和TAP1、TAP2、HLA、CD8的表达情况，分析其与临床病理特征的关系。进一步采用χ²检验或Fisher精确检验、Spearman秩相关检验分析HPV感染与上述蛋白表达的相关性，采用Kaplan-Meier进行生存分析，Cox比例风险回归模型进行多因素生存分析。结果　P16在喉鳞状细胞癌中的阳性表达率为11.9%（10/84），在癌旁正常组织中为阴性表达；CD8在喉鳞状细胞癌组织中的阳性率为38.1%（32/84），低于癌旁正常组织［56.0%（47/84）］，TAP1、TAP2、HLA在喉鳞状细胞癌组织中的阳性率均低于癌旁正常组织［41.7%（35/84）比69.0%（58/84）、29.8%（25/84）比56.0%（47/84）、42.8%（36/84）比57.1%（48/84）］，其中，TAP2在癌和癌旁正常组织中的表达差异有统计学意义（χ²=5.80，P<0.05）。喉鳞状细胞癌组织中CD8的表达与临床分期有关，差异有统计学意义（χ²=6.57，P<0.05）；而TAP1、TAP2、HLA、P16的表达与临床病理因素无关。Spearman关联性分析结果提示TAP1表达与TAP2、CD8呈正相关（r=0.295、0.232，均P<0.05），HLA的表达与CD8的表达呈正相关（r=0.232，P<0.05）。结论　TAP1、TAP2、HLA、CD8在喉鳞状细胞癌组织中低表达，提示肿瘤可能通过下调TAP1、TAP2导致HLA表达异常，从而抑制CD8免疫应答过程，进而抑制机体免疫反应，为肿瘤免疫逃逸机制提供理论支持。

关键词:

喉鳞状细胞癌, 抗原加工相关转运体, 人乳头瘤病毒, 肿瘤免疫