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

Autor: Tao Tian, Ai-Min Jiang, Xiao Fu, Zhiping Ruan, Na Liu, Yu Yao, Meng-Di Ren, Xuan Liang, Jingjing Wang, Xiaoqiang Zheng, Huan Gao
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
DNA Mutational Analysis
Datasets as Topic
Kaplan-Meier Estimate
Tumor mutation burden (TMB)
CD8-Positive T-Lymphocytes
Malignancy
Polymorphism
Single Nucleotide
Risk Assessment
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
Immune system
Tumor-Associated Macrophages
Biomarkers
Tumor
Tumor Microenvironment
Humans
Medicine
Missense mutation
Prospective Studies
IRGs
Models
Genetic
Immune-related genes (IRGs)
Squamous Cell Carcinoma of Head and Neck
business.industry
Gene Expression Profiling
Head and neck cancer
Models
Immunological
Head and neck squamous cell carcinoma (HNSCC)
General Medicine
TCGA
Prognosis
medicine.disease
Head and neck squamous-cell carcinoma
Gene Expression Regulation
Neoplastic
Immune cell infiltration
Head and Neck Neoplasms
Mutation
Cancer research
030211 gastroenterology & hepatology
business
CD8
Research Paper
FAT1
Zdroj: International Journal of Medical Sciences
ISSN: 1449-1907
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: