Background. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods. Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results. In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion. In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

中文翻译：

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口腔鳞状细胞癌预后预测的免疫相关风险特征的鉴定

背景。口腔鳞状细胞癌 (OSCC) 是最常见的口腔癌类型，它仍然是头颈癌患者发病率和死亡率的主要原因。然而，很少研究关键的免疫相关特征及其预后价值。材料和方法。基因差异分析用于测量组间基因表达的差异。相关分析用于评估基因表达水平与免疫相关风险评分/DNA甲基化水平之间的关联。基因集富集分析 (GSEA) 用于鉴定由那些鉴定的差异表达基因 (DEG) 富集的途径或细胞类型。结果. 在这项研究中，我们确定了四种免疫相关基因特征，包括CTSG、TNFRSF4、LCORL和PLAU，这与癌症基因组图谱 (TCGA) OSCC 队列中 OSCC 患者的总生存期显着相关。此外，这四种免疫相关特征在 OSCC 和非肿瘤组织之间存在差异表达。按免疫相关风险评分分层的两组（高风险和低风险）具有显着不同的 OS 和死亡率。这些免疫相关特征的基因表达模式和预后价值也在两个独立的验证队列中得到验证。此外，高风险组中下调的基因（在低风险组中也上调）在 2 型 T 辅助细胞（Th2）、浆细胞样树突状细胞（pDC）的细胞类型特异性特征中显着富集，和记忆B细胞。相比之下，结论。总之，免疫相关特征具有预测 OSCC 患者风险的潜力。此外，本研究还提高了我们对 OSCC 中生长因子受体途径与免疫细胞浸润之间关联的理解。