A Novel Immune-Related Prognostic Signature in Head and Neck Squamous Cell Carcinoma

Yi Zhang,Jie Wang,Qiang Zhou,Qingquan Hua,Hongliang Zhong,Ping Chen,Hongyan Wang

doi:10.3389/fgene.2021.570336

Abstract

The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, very limited robust and reliable immunological biomarkers have been developed that are capable of estimating prognosis in HNSCC patients. In this study, we aimed to identify the effects of novel immune-related gene signatures (IRGs) that can predict HNSCC prognosis. Based on gene expression profiles and clinical data of HNSCC patient cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, a total of 439 highly variable expressed immune-related genes (including 239 upregulated and 200 downregulated genes) were identified by using differential gene expression analysis. Pathway enrichment analysis indicated that these immune-related differentially expressed genes were enriched in inflammatory functions. After process screening in the training TCGA cohort, six immune-related genes (PLAU, STC2, TNFRSF4, PDGFA, DKK1, and CHGB) were significantly associated with overall survival (OS) based on the LASSO Cox regression model. Integrating these genes with clinicopathological features, a multivariable model was built and suggested better performance in determining patients’ OS in the testing cohort, and the independent validation cohort. In conclusion, a well-established model encompassing both immune-related gene signatures and clinicopathological factors would serve as a promising tool for the prognostic prediction of HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is one of the world’s leading causes of morbidity and mortality, accounting for about 4% of all cancers (Riba et al, 2019)
The gene expression matrix of the The Cancer Genome Atlas (TCGA)-head and neck squamous cell carcinoma (HNSCC) dataset was analyzed to identify differentially expressed genes (DEGs), this matrix consisted of 502 HNSCC samples and 44 adjacent non-tumor samples
A total of 5790 DEGs were identified with | log2FC| > 1 and an false discovery rate (FDR) < 0.05, including 3532 upregulated genes and 2258 downregulated genes

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the world’s leading causes of morbidity and mortality, accounting for about 4% of all cancers (Riba et al, 2019). HNSCC accounts for 95% of head and neck cancers and occurs in the mouth, oropharynx, hypopharynx, or throat (Haddad and Shin, 2008). The 5-year survival rate for HNSCC patients is only 63%, mainly because local recurrence or distant metastasis occurs in approximately 80–90% of patients with advanced HNSCC. Epstein Barr virus (EBV) infection is one of the main causes of nasopharyngeal carcinoma (Turunen et al, 2017). These studies suggest that the occurrence of HNSCC tumors is a multi-step, and multi-factorial process

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