Department of Head and Neck Surgery Section II, the Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China.
Radiation Therapy Center, the Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China.
Sci Rep. 2020 Apr 14;10(1):6395. doi: 10.1038/s41598-020-63148-8.
Head and neck cancer is the sixth most common malignancy around the world, and 90% of cases are squamous cell carcinomas. In this study, we performed a systematic investigation of the immunogenomic landscape to identify prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC). We analyzed the expression profiles of immune-related genes (IRGs) and clinical characteristics by interrogating RNA-seq data from 527 HNSCC patients in the cancer genome atlas (TCGA) dataset, including 41 HPV+ and 486 HPV- samples. We found that differentially expressed immune genes were closely associated with patient prognosis in HNSCC by comparing the differences in gene expression between cancer and normal samples and performing survival analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of the differentially expressed immunogenomic prognosis-related genes. Two additional cohorts from the Oncomine database were used for validation. 65, 56 differentially expressed IRGs was associated with clinical prognosis in total and HPV samples, respectively. Furthermore, we extracted 10, 11 prognosis-related IRGs from 65, 56 differentially expressed IRGs, respectively. They were significantly correlated with clinical prognosis and used to construct the prognosis prediction models. The multivariable ROC curves (specifically, the AUC) were used to measure the accuracy of the prognostic models. These genes were mainly enriched in several gene ontology (GO) terms related to immunocyte migration and receptor and ligand activity. KEGG pathway analysis revealed enrichment of pathways related to cytokine-cytokine receptor interactions, which are primarily involved in biological processes. In addition, we identified 63 differentially expressed transcription factors (TFs) from 4784 differentially expressed genes, and 16 edges involving 18 nodes were formed in the regulatory network between differentially expressed TFs and the high-risk survival-associated IRGs. B cell and CD4 T cell infiltration levels were significantly negatively correlated with the expression of prognosis-related immune genes regardless of HPV status. In conclusion, this comprehensive analysis identified the prognostic IRGs as potential biomarkers, and the model generated in this study may enable an accurate prediction of survival.
头颈部癌是全球第六大常见恶性肿瘤，其中 90%为鳞状细胞癌。本研究通过对癌症基因组图谱（TCGA）数据集内 527 例头颈部鳞状细胞癌（HNSCC）患者的 RNA-seq 数据进行免疫基因组景观的系统分析，以确定其预后生物标志物。我们分析了免疫相关基因（IRGs）的表达谱和临床特征，包括 41 例 HPV+和 486 例 HPV-样本。我们发现，通过比较癌症和正常样本之间基因表达的差异并进行生存分析，差异表达的免疫基因与 HNSCC 患者的预后密切相关。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析以注释差异表达的免疫基因组预后相关基因的生物学功能。我们还使用 Oncomine 数据库中的另外两个队列进行验证。在总样本和 HPV 样本中，分别有 65 个和 56 个差异表达的 IRG 与临床预后相关。此外，我们从这 65 个和 56 个差异表达的 IRG 中分别提取了 10 个和 11 个预后相关的 IRG。这些基因与临床预后显著相关，可用于构建预后预测模型。多变量 ROC 曲线（特别是 AUC）用于衡量预后模型的准确性。这些基因主要富集在与免疫细胞迁移和受体及配体活性相关的几个基因本体（GO）术语中。KEGG 通路分析显示，与细胞因子-细胞因子受体相互作用相关的途径富集，这些途径主要涉及生物学过程。此外，我们从 4784 个差异表达基因中鉴定出 63 个差异表达转录因子（TF），并在差异表达 TF 与高风险生存相关的 IRG 之间形成了 16 个涉及 18 个节点的调控网络。无论 HPV 状态如何，B 细胞和 CD4 T 细胞浸润水平与预后相关免疫基因的表达呈显著负相关。总之，本研究全面分析确定了预后相关的 IRG 作为潜在的生物标志物，且本研究中生成的模型可准确预测患者的生存情况。
