目的:目的是检测NKG2A及其配体HLA-E的表达水平特征,免疫检查站的新成员,晚期喉癌及其临床病理意义。
方法:我们利用肿瘤免疫评估资源(TIMER)数据库以及石蜡包埋组织样本的免疫组织化学和qRT-PCR分析,分析了多种类型肿瘤中HLA-E和NKG2A的表达水平。揭示晚期喉癌中临床病理因素与这两种蛋白表达的相关性及其预后意义。
结果:KLRC1(NKG2A的编码基因)和HLA-E在各种人类癌症中的表达明显高于正常组织。HNSCC也包括在内。KLRC1在不同HPV患者亚组中差异表达,在HPV阳性组中有较高的表达。与此一致,免疫组织化学结果也显示这两种蛋白在肿瘤组织中的高表达。此外,免疫组织化学染色还显示了对NKG2A阳性细胞在肿瘤组织中分布的偏好。临床病理分析还显示,HPV阳性组浸润喉癌组织的NKG2A阳性细胞密度大于HPV阴性组。预后分析表明,该免疫检查点的表达不影响患者的总体生存时间。但HLA-E高表达与患者局部复发显著相关.
结论:研究结果表明,晚期喉癌中HLA-E和NKG2A的表达水平上调。浸润肿瘤的NKG2A阳性细胞主要分布在癌巢,而浸润细胞数量可能受HPV调控。高表达的HLA-E可能促进晚期喉癌患者的局部复发。
OBJECTIVE: The purpose was to detected features of the expression levels of
NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance.
METHODS: We analyzed the expression levels of HLA-E and
NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance.
RESULTS: KLRC1 (the coding gene of
NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of
NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients.
CONCLUSIONS: The findings suggest that the expression levels of HLA-E and
NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.