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

Abstract

Background: 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. Growing evidence has demonstrated that the immune system plays a crucial role in the development and progression of HNSCC. The goal of our study was to develop an immune-related signature for accurately predicting the survival of HNSCC patients. Methods: Gene expression profiles were established from a total of 546 HNSCC and normal tissues to establish a training set and 83 HNSCC tissues for a validation set. Differentially expressed prognostic immune genes were identified by univariate Cox regression analysis and a corresponding network of differentially expressed transcription factors (TFs) were identified using Cytoscape. The immune-related gene signature was established and validated by univariate Cox regression analysis, least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses. In addition, the prognostic value of the immune-related signature was analyzed by survival and Cox regression analysis. Finally, the correlation between the immune-related signature and the immune microenvironment was established.Results: In this study, the TF-mediated network revealed that Foxp3 plays a central role in the regulatory mechanism of most immune genes. A prognostic signature based on 10 immune-related genes, which divided patients into high and low risk groups, was developed and successfully validated using two independent databases. Our prognostic signature was significantly related to worse survival and predicted prognosis in patients with different clinicopathological factors. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature may act as an independent factor for predicting the survival of HNSCC patients. ROC analysis also revealed that our signature had superior predictive value compared with TNM stage. As for the immune microenvironment, our signature showed a positive correlation with activated mast cells and M0 macrophages, a negative correlation with Tregs, and immune checkpoint molecules PD-1 and CLTA-4. Conclusions: Our study established an immune-related gene signature, which not only provides a promising biomarker for survival prediction, but may be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.

Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives

“…As mentioned earlier, SCCHN is genetically heterogeneous, which has complicated the search for an evident immune-related gene signature. Multiple studies investigated different sets of immune genes signatures to predict prognosis in the population while also tailoring the use of immunotherapy through assigning different immune-gene based subgroups to various immunotherapy based strategies [ 7 , 140 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 ]. Results from these studies have generated an immune-related gene panel or signature based on 10 to 27 different genes (cfr.…”