Identification and Validation of 17-lncRNA Related to Regulatory T Cell Heterogeneity as a Prognostic Signature for Head and Neck Squamous Cell Carcinoma

Abstract

Successful eradication of tumors by the immune system depends on generation of antigen-specific T cells that migrate to tumor sites and kill cancerous cells. However, presence of suppressive Treg populations inside tumor microenvironment hinders effector T cell function and decreases antitumor immunity. In this study we independently evaluated and confirmed prognostic signature of 17-Treg-related-lncRNA. Immune cell infiltration analysis using 17-lncRNA signature as a probe, accurately described Treg populations in tumor immune microenvironment. 17-lncRNA signature model predicted prognosis with excellent accuracy in all three cohorts: training cohort (AUC=0.82), testing cohort (AUC=0.61) and total cohort (AUC=0.72). The Kaplan-Meier analysis confirmed that the overall survival of patients in the low-risk group was significantly better than those in the high-risk group(P<0.001). CIBERSORT analysis confirmed that low risk group had higher infiltration of tumor killer CD8 T cells, memory activated CD4 T cells, follicular helper T cells and T cells regulatory (Tregs), and lower expression of M0 macrophages and Mast cells activated. These results indicate that the 17-lncRNA signature is a novel prognostic and support the use of lncRNA as a stratification tool to help guide the course of treatment and clinical decision making in patients at high risk of HNSCC.

Keywords: head and neck squamous cell carcinoma; immune cell infiltration; long non-coding RNA; prognostic signature; regulatory T cell heterogeneity.