Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

Yangyang She; Xiangbo Kong; Yaping Ge; Ping Yin; Zhiyong Liu; Jieyu Chen; Feng Gao; Silian Fang

doi:10.1186/s12935-020-1104-7

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

Cancer Cell Int. 2020 Jan 17:20:22. doi: 10.1186/s12935-020-1104-7. eCollection 2020.

Authors

Yangyang She¹, Xiangbo Kong², Yaping Ge¹, Ping Yin¹, Zhiyong Liu¹, Jieyu Chen¹, Feng Gao^{3

4}, Silian Fang^{1

5}

Affiliations

¹ 1Department of Oral and Maxillofacial Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26 Yuancun Erheng Rd, Guangzhou, 510655 Guangdong China.
² 2Department of Stomatology, Sun Yat‑sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong China.
³ 3Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26 Yuancun Erheng Rd, Guangzhou, 510655 Guangdong China.
⁴ 4Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26 Yuancun Erheng Rd, Guangzhou, 510655 Guangdong China.
⁵ 5Section of Oral and Maxillofacial Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI 48109 USA.

Abstract

Background: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis.

Methods: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration.

Results: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01).

Conclusion: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

Keywords: Head and neck squamous cell carcinoma (HNSCC); Immune related gene signature (IRGS); Prognosis.