Discovery and Verification of an Immune-Related Gene Pairs Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma.

Jiqiang He,Mingming Han,Xinqi Fang

doi:10.3389/fgene.2021.654657

Abstract

The study of IRGPs to construct the prognostic signature in head and neck squamous cell carcinoma (HNSCC) has not yet elucidated. The objective of this study was to explore a novel model to predict the prognosis of HNSCC patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were set as training and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) and time-dependent ROC were employed to screen the highest frequency immune-related gene pairs (IRGPs) and their best cut-off value. Survival analysis, Cox regression analysis were applied to discover the effects of selected IRGPs signature on survival outcomes. The immune cell proportions were deconvoluted by the CIBERSORT method. After a couple of filtering, we obtained 22 highest frequency IRGPs. The overall survival time of HNSCC patients with a high score of IRGPs was shorter as compared to the ones with a low score in two independent datasets (P < 0.001). Six kinds of immune cells were found to be differentially distributed in the two different risk groups of HNSCC patients (P < 0.001). GO and GSEA analysis showed these differentially expressed genes enriched in multiple molecular functions. The new IRGPs signature probably confers a new insight into the prognosis prediction of HNSCC patients.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers globally, and more than 600,000 cases are diagnosed annually (Leemans et al, 2011)
The Kaplan Merrier analysis showed that patients with a high score of immune-related gene pairs (IRGPs) had been predicted a poorer outcome as opposed to a low score of IRGPs (P < 0.001, Figure 2B), which was further validated in the GSE65858 cohort (P < 0.05, Figure 2C) and GSE2379 (P = 0.032, Figure 2D)
To test whether the effect of IRGPs on head and neck squamous cell carcinoma (HNSCC) prognosis is independent of clinical parameters like age, clinical stage, lymph node status, etc., univariable and multiple variable Cox proportional regression analysis were performed

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers globally, and more than 600,000 cases are diagnosed annually (Leemans et al, 2011). Local or distant metastasis is the major factor for cancer-associated death (Huang et al, 2018). Despite multimodal treatments, such as surgery, chemoradiotherapy, and targeted therapies, the 5-year survival rate of HNSCC patients remains poor (Li et al, 2020; Zhang et al, 2020). Even patients with the same clinical symptoms, TNM stage, and treatments would have different prognoses (Karam and Raben, 2019). The inaccurate effects of the TNM stage on predicting the prognosis

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