Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Int J Med Sci. 2021 Jan 1;18(1):226-238. doi: 10.7150/ijms.51064. eCollection 2021.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. , , and were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.
头颈部鳞状细胞癌（HNSCC）是全球第六大常见恶性肿瘤，HNSCC 的预后仍然不容乐观。大量研究表明，肿瘤突变负担（TMB）可预测多种肿瘤的生存结局。本研究旨在探讨这些患者的 TMB 和免疫细胞浸润情况，并构建免疫相关基因（IRGs）预后模型。从癌症基因组图谱（TCGA）数据库中获取了 546 例 HNSCC 患者的表达数据。所有患者分为高 TMB 和低 TMB 组，进一步分析 TMB 与临床相关性。使用 R 软件包 limma 识别差异表达基因（DEGs）。进行功能富集分析以确定两组之间显著富集的途径。采用 CIBERSORT 算法计算 22 种白细胞亚群的丰度。通过多变量 Cox 回归分析构建 IRGs 预后模型。错义突变和单核苷酸变异（SNV）是 HNSCC 中最主要的突变类型。 、 、 和 是突变频率最高的基因。TMB 较高的患者观察到生存结局较差。TMB 相关 DEGs 的功能分析表明，鉴定的 DEGs 主要涉及剪接体、RNA 降解、蛋白酶体和 RNA 聚合酶途径。我们观察到巨噬细胞、CD8+T 细胞和 CD4+记忆 T 细胞是 HNSCC 中最常见浸润的免疫细胞亚群。最后，构建了一个 IRGs 预后模型，ROC 曲线的 AUC 为 0.635。我们的结果表明，高 TMB 与 HNSCC 患者的不良预后相关。构建的模型对这些患者的预后具有潜在的预测价值，需要在大规模前瞻性研究中进一步验证。
