Integrated Analysis of RNA-Binding Proteins Associated With the Prognosis and Immunosuppression in Squamous Cell Carcinoma of Head and Neck.

Guangsheng Hu,Hong Peng,Zhifeng Liu,Yaya Wang,Shuyan Li,Jing Yu,Qingshan Jiang,Jing Yang,Yanhua Tang,Lijun Liu

doi:10.3389/fgene.2020.571403

Abstract

RNA-binding proteins (RBPs) interacting with target RNAs play essential roles in RNA metabolism at the post-transcription level. Perturbations of RBPs can accelerate cancer development and cause dysregulation of the immune cell function and activity leading to evade immune destruction of cancer cells. However, few studies have systematically analyzed the potential prognostic value and functions of RBPs in squamous cell carcinoma of head and neck (SCCHN). Here, for the first time, we comprehensively identified 92 differentially expressed RBPs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model was constructed with six RBPs, including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2, and validated by the TCGA test set, the TCGA all set, and the GEO data set. In addition, the risk score was related to the clinical stage, T classification, and N classification. Furthermore, the high-risk score was significantly correlated with immunosuppression, and low expression of EZH2 and AZGP1 and high expression of IGF2BP2 were the main factors. Thus, the risk model may serve as a prognostic signature and offer highlights for individualized immunotherapy in SCCHN patients.

Highlights

Squamous cell carcinoma of head and neck (SCCHN) represents the sixth most common malignancy, with increasing incidence and over 300,000 deaths annually (Ferlay et al, 2015; Siegel et al, 2020)
The results showed that the differentially expressed RBPs (DERBPs) might be related to measles, influenza A, hepatitis C, RNA transport, Epstein–Barr virus infection, mRNA surveillance pathway, cytosolic DNA-sensing pathway, RIGI-like receptor signaling pathway, and RNA degradation
We constructed a prognosis risk model in the training set with six RNA-binding proteins (RBPs), including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2 (Figure 1C), which showed a robust performance for predicting prognosis compared with clinical parameters in training and multiple validation sets (Figures 4–6)

Summary

Introduction

Squamous cell carcinoma of head and neck (SCCHN) represents the sixth most common malignancy, with increasing incidence and over 300,000 deaths annually (Ferlay et al, 2015; Siegel et al, 2020). RBPs Integrated Analysis for SCCHN treatments, including surgery, chemotherapy, and radiotherapy, the 5-year survival rate has not notably improved (Cramer et al, 2019). 1542 human RBPs, accounting for 7.5% of all protein-coding genes, interacting with all known RNA types have been identified utilizing deepsequencing approaches (Gerstberger et al, 2014; Beckmann et al, 2015), which provide a rare opportunity for systematic analysis of RBP genes in cancers. Few studies have comprehensively analyzed the relationship between RBPs and the prognosis of squamous cell carcinoma of head and neck (SCCHN)

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Discussion

Conclusion