Zhang Shoujing, Zhang Wenyi, Zhang Jian
Department of Oral and Maxillofacial Surgery, Tianjin Medical University School and Hospital of Stomatology, Tianjin, China.
Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin, China.
Front Genet. 2022 Jul 22;13:938611. doi: 10.3389/fgene.2022.938611. eCollection 2022.
CD8 T cells, a critical component of the tumor immune microenvironment, have become a key target of cancer immunotherapy. Considering the deficiency of robust biomarkers for head and neck squamous cell carcinoma (HNSCC), this study aimed at establishing a molecular signature associated with CD8+T cells infiltration. Single-cell RNA sequencing data retrieved from the Gene Expression Omnibus (GEO) database was analyzed to obtain the different cell types. Next, the cell proportions were investigated through deconvolution of RNA sequencing in the Cancer Genome Atlas (TCGA) database, and then the immune-related genes (IRGs) were identified by weighted gene co-expression network analysis (WGCNA). LASSO-Cox analysis was employed to establish a gene signature, followed by validation using a GEO dataset. Finally, the molecular and immunological properties, and drug responses between two subgroups were explored by applying "CIBERSORT", "ESTIMATE", and single sample gene set enrichment analysis (ssGSEA) methods. A total of 215 differentially expressed IRGs were identified, of which 45 were associated with the overall survival of HNSCC. A risk model was then established based on eight genes, including , , , , , , , and . The low-risk group presented higher infiltration of memory activated CD4 T cells, CD8 T cells, and plasma cells, as well as a higher immune score, suggesting that they could benefit more from immunotherapy. On the other hand, the high-risk group showed higher abundance of activated mast cells and M2 macrophages, as well as a lower immune score. It was evident that the 8-gene signature could accurately predict HNSCC prognosis and thus it may serve as an index for clinical treatment.
CD8 T细胞是肿瘤免疫微环境的关键组成部分，已成为癌症免疫治疗的关键靶点。鉴于头颈部鳞状细胞癌（HNSCC）缺乏强大的生物标志物，本研究旨在建立一种与CD8+T细胞浸润相关的分子特征。分析从基因表达综合数据库（GEO）检索到的单细胞RNA测序数据，以获得不同的细胞类型。接下来，通过对癌症基因组图谱（TCGA）数据库中的RNA测序进行反卷积来研究细胞比例，然后通过加权基因共表达网络分析（WGCNA）鉴定免疫相关基因（IRG）。采用LASSO - Cox分析建立基因特征，随后使用GEO数据集进行验证。最后，应用“CIBERSORT”、“ESTIMATE”和单样本基因集富集分析（ssGSEA）方法探索两个亚组之间的分子和免疫学特性以及药物反应。共鉴定出215个差异表达的IRG，其中45个与HNSCC的总生存期相关。然后基于8个基因建立了一个风险模型，包括 、 、 、 、 、 、 和 。低风险组表现出记忆激活的CD4 T细胞、CD8 T细胞和浆细胞的浸润更高，以及免疫评分更高，这表明他们可能从免疫治疗中获益更多。另一方面，高风险组显示活化肥大细胞和M2巨噬细胞的丰度更高，以及免疫评分更低。显然，这8个基因的特征可以准确预测HNSCC的预后，因此它可以作为临床治疗的一个指标。
