Foshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, China.
J Immunol Res. 2021 Aug 25;2021:6203759. doi: 10.1155/2021/6203759. eCollection 2021.
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.
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).
In this study, we identified four immune-related gene signatures, including , , , and , 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.
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.
口腔鳞状细胞癌（OSCC）是最常见的口腔癌类型，仍是头颈部癌症患者发病率和死亡率的主要原因。然而，关键的免疫相关特征及其预后价值很少被研究。
采用基因差异分析测量两组间基因表达的差异。采用相关性分析评估基因表达水平与免疫相关风险评分/DNA 甲基化水平之间的相关性。采用基因集富集分析（GSEA）鉴定由差异表达基因（DEG）鉴定的途径或细胞类型。
本研究从癌症基因组图谱（TCGA）OSCC 队列中确定了四个与 OSCC 患者总生存期显著相关的免疫相关基因特征，包括 、 、 、 。此外，这些四个免疫相关特征在 OSCC 与非肿瘤组织之间存在差异表达。根据免疫相关风险评分分层的两组（高风险和低风险）在 OS 和死亡率方面有显著差异。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）和记忆 B 细胞的细胞类型特异性特征中显著富集。相反，高评分组上调的基因在生长因子受体相关信号通路中富集，如 VEGFA-VEGFR2 信号通路、PI3K-Akt 信号通路、焦点黏附-PI3K-Akt-mTOR 信号通路和 PDGF 通路，表明这些通路与免疫细胞浸润呈负相关。
总之，免疫相关特征有可能预测 OSCC 患者的风险。此外，本研究还提高了我们对生长因子受体途径与 OSCC 中免疫细胞浸润之间关联的理解。
