Immune Landscape of the B7 and TNFR Families in Oral Squamous Cell Carcinoma
Immune Landscape of the B7 and TNFR Families in Oral Squamous Cell Carcinoma
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口腔鳞状细胞癌中 B7 和 TNFR 家族的免疫景观
DOI：
10.3290/j.cjdr.a44747
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发表时间：
2020-01-01
影响因子：
0.9
通讯作者：
Cheng, Bin
中科院分区：
文献类型：
--
作者：
Ren, Xian Yue;Chen, Xi Juan;Cheng, Bin
目的：了解两个主要的共刺激和共抑制途径的免疫分子景观（B7和TNPR家族）在口腔鳞状细胞癌中的作用。B7家族成员（CD 80、CD 86、CD 274、ICOSLG、CD 276、VTCN 1、NCR-3LG 1、HHLA 2和PDCD 1 LG 2）和INF家族成员共刺激和共抑制信号通路（TNFSF 4、CD 40、CD 70、TNFSF 9、TNFSF 14和TNFSF 18）在口腔鳞状细胞癌中的表达。使用在线工具UCSC Xena和cBioPortal获得口腔鳞状细胞癌患者的临床参数、mRNA水平、突变、DNA拷贝数改变和甲基化水平。采用斯皮尔曼相关分析确定mRNA水平和甲基化水平之间的相关性。KaplanMeier生存分析进行检查mRNA表达水平和总survival.Results之间的关系：与正常口腔上皮组织相比，约23.1%的患者显示B7表达上调，15.3%的患者显示上调TNFR表达在口腔鳞状细胞癌，与CD 274（PD-L1）上调是最常见的改变。突变和拷贝数改变对B7和TNFR表达的影响很小。B7和TNFR基因mRNA水平与其甲基化水平呈负相关。CD 274高表达的口腔鳞状细胞癌患者生存率低，而CD 276或HHLA 2高表达的口腔鳞状细胞癌患者生存率高。结论：本研究阐明了B7和TNFR基因在口腔鳞状细胞癌中的分子结构，为临床治疗提供了新的策略。
Objective: To understand the immune molecular landscapes of the two major costimulatory and coinhibitory pathways (B7 and TNPR families) in oral squamous cell carcinoma.Methods: The B7 family members (CD80, CD86, CD274, ICOSLG, CD276, VTCN1, NCR-3LG1, HHLA2 and PDCD1LG2) and INFRfamily members (TNFSF4, CD40, CD70, TNFSF9, TNFRSF14 and TNFSF18) were used to analyse the costimulatory and coinhibikny pathway alterations in oral squamous cell carcinoma. The online tools UCSC Xena and cBioPortal were used to derive oral squamous cell carcinoma patients'clinical parameters, mRNA levels, mutations, DNA copy number alterations and methylation levels. The correlations between mRNA levels and methylation levels were determined using Spearman correlation analysis. A Kaplan Meier survival analysis was performed to examine the relationships between mRNA expression levels and overall survival.Results: Compared with normal oral epithelial tissues, approximately 23.1% of patients showed upregulation of B7 expression and 15.3% showed upregulation of TNFR expression in oral squamous cell carcinoma, with CD274 (PD-L1) upregulation being the most common alteration. Mutations and copy number alterations were shown to have little effect on B7 and TNFR expression. The mRNA levels of B7 and TNFR genes were negatively correlated with their methylation levels. Furthermore, oral squamous cell carcinoma patients with high expression levels of CD274 showed poor overall survival, while those with high expression levels of CD276 or HHLA2 showed good clinical outcomes.Conclusion: This study elucidated the molecular landscapes of the B7 and TNFR genes in oral squamous cell carcinoma, which could provide a novel strategy for clinical therapy.