Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Abstract

Background: 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. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: 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. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 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. Conclusions: 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.

Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes, Signaling Pathways, and Immune Activity

“…Patients with bladder cancer with higher TMB levels have a better prognosis ( Fan et al, 2020 ; Mi et al, 2020 ; Wu et al, 2020 ). However, in head and neck squamous cell carcinoma and melanoma, high TMB can lead to a shorter survival period, which may be related to infiltrating immune cells ( Jiang et al, 2020 , 2021 ). The above results indicate that the cellular components of the tumor involved in the immune response are complex, which leads to different immunotherapy effects in patients.…”

A Robust Prognostic Gene Signature Based on eRNAs-Driven Genes in Prostate Cancer

“…We considered this to be MSI high in the high-risk group and MSI low in the low-risk group, due to the tumor’s disrupted function during DNA damage repair leading to increased gene instability, which is consistent with the results of TMB in the high and low risk groups. Jiang et al (2021) found that patients with high TMB had worse survival outcomes than those with low TMB. We believe that this finding may account for the longer DFS in the low-risk group, compared to the high-risk group.…”

Mutational profiling of low‐grade gliomas identifies prognosis and immunotherapy‐related biomarkers and tumour immune microenvironment characteristics

“…42 TMB and MSI have been considered new biomarkers of immunotherapy response and potential predictors of response to immune checkpoint inhibitors (ICIs). 43,44 The TMB score analysis revealed that the expression level of six survival-related mutated genes was significantly positively correlated with TMB in…”