Research Paper Volume 13, Issue 8 pp 11507—11527

A novel comprehensive immune-related gene signature as a promising survival predictor for the patients with head and neck squamous cell carcinoma

Ruihua Fang1,2,3, *, , Muhammad Iqbal1,2,3, *, , Lin Chen1,2,3, *, , Jing Liao4, , Jierong Luo5, , Fanqin Wei1,2,3, , Weiping Wen1,2,3,4, , Wei Sun1,2,3, ,

  • 1 Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
  • 2 Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
  • 3 Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou 510080, Guangdong, P.R. China
  • 4 Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, Guangdong, P.R. China
  • 5 Department of Anesthesia, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou 510080, Guangdong, P.R. China
* Equal contribution

Received: December 18, 2020       Accepted: March 3, 2021       Published: April 17, 2021
How to Cite

Copyright: © 2021 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. The TNM stage is not satisfactory for individualized prognostic assessment and it does not predict response to therapy. In the present study, we downloaded the gene expression profiles from TCGA database to establish a training set and GEO database for a validation set. In the training set, we developed an 10 immune-related genes signature which had superior predictive value compared with TNM stage. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature might act as an independent factor for predicting the survival of HNSCC patients. As for the immune microenvironment, our results showed higher immune checkpoint expression (CLTA-4 and PD-1) in low-risk group which might reflect a positive immunotherapy response. Thus, our signature not only provided a promising biomarker for survival prediction, but might be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.


HNSCC: Head and neck squamous cell carcinoma; AJCC: American Joint Committee on Cancer; TFs: Transcription factors; LASSO: Least absolute shrinkage and selector operation; HPV: Human papillomavirus; qRT-PCR: quantitative real-time polymerase chain reaction; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; PD-1: Programmed cell death protein-1; PD-L1: Programmed cell death-ligand 1; TCGA: The Cancer Genome Atlas; GEO: Group on Earth Observations; GSEA: Gene Set Enrichment Analysis; OS: Overall survival; IRGs: Immune-related genes; ImmPort: Immunology Database and Analysis Portal; DEGs: Differentially expressed genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; HR: Hazard Ratio; ROC: Operating characteristic curve; BP: Biological process; MF: Molecular function; CC: Cell component; AUCs: Area under the ROC curve; Tregs: Regulatory T cells.