Identification of Novel Biomarkers for Predicting Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma Based on ceRNA Network and Immune Infiltration Analysis

Abstract

Objectives. Patients with head and neck squamous cell carcinoma (HNSCC) have poor prognosis and show poor responses to immune checkpoint (IC) inhibitor (ICI) therapy. Competing endogenous RNA (ceRNA) networks, tumor-infiltrating immune cells (TIICs), and ICIs may influence tumor prognosis and response rates to ICI therapy. This study is aimed at identifying prognostic and IC-related biomarkers and key TIIC signatures to improve prognosis and ICI therapy response in HNSCC patients. Methods and Results. Ninety-five long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and 1746 mRNAs were identified using three independent methods. We constructed a ceRNA network and estimated the proportions of 22 immune cell subtypes. Ten ceRNAs were related to prognosis according to Kaplan–Meier analysis. Two risk signatures based, respectively, on nine ceRNAs (ANLN, CFL2, ITGA5, KDELC1, KIF23, NFIA, PTX3, RELT, and TMC7) and three immune cell types (naïve B cells, neutrophils, and regulatory T cells) via univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analyses could accurately and independently predict the prognosis of HNSCC patients. Key mRNAs in the ceRNA network were significantly correlated with naïve B cells and regulatory T cells and with stage, grade, and immune and molecular subtype. Eight IC genes exhibited higher expression in tumor tissues and were correlated with eight key mRNAs in the ceRNA network in HNSCC patients with different HPV statuses according to coexpression and TIMER 2.0 analyses. Most drugs were effective in association with expression of these key signatures (ANLN, CFL2, ITGA5, KIF23, NFIA, PTX3, RELT, and TMC7) based on GSCALite analysis. The prognostic value of key biomarkers and associations between key ceRNAs and IC genes were validated using online databases. Eight key ceRNAs were confirmed to predict response to ICI in other cancers based on TIDE analysis. Conclusions. We constructed two risk signatures to accurately predict prognosis in HNSCC. Key IC-related signatures may be associated with response to ICI therapy. Combinations of ICIs with inhibitors of eight key mRNAs may improve survival outcomes of HNSCC patients.

Cervical cancer immune infiltration microenvironment identification, construction of immune scores, assisting patient prognosis and immunotherapy

“…IL1B can also enhance the signal transduction of CTLA4, and targeting the IL1B-CTLA4 axis can effectively inhibit the occurrence of metastatic and recurrent colon cancer (69). ITGA5 is a crucial immunotherapy predictive target that is thought to be crucial in the incidence and progression of many cancers (70)(71)(72). CST7 is associated with activation of CD4T and CD8T cells in liver cancer (73).…”

Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma

“…TMC7 was identi ed as a potential prognostic biomarker for pancreatic cancer, and its high expression was associated with a poor prognosis (33). An early study said TMC7 expression negatively correlated with CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT expression in head and neck squamous cell carcinoma (45). In contrast, our research came to the opposite conclusion in RCCC.…”

Identification of a novel ceRNA network related to prognosis and immunity in HNSCC based on integrated bioinformatic investigation

“…Different types of cancer have different proportions of infiltrating immune cells, which affects immunological response and prognosis 7 . Recent research has shown that ceRNA networks participate in tumor cell-immune system communication, and several molecular signatures are biomarkers for this crosstalk 8,9 www.nature.com/scientificreports/ the coinhibitory receptor programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), which have revolutionized cancer therapy for the past few years. The TME also affects the degree of the immune checkpoint inhibition response in HNSCC 10 .…”

“…Earlier research into ceRNAs in HNSCC found many RNAs linked to patients OS [30][31][32] . Guo et al constructed two risk signatures on nine ceRNAs (ANLN, CFL2, ITGA5, KDELC1, KIF23, NFIA, PTX3, RELT, and TMC7) and three immune cell types (naïve B cells, neutrophils, and regulatory T cells) 9 . These immune cells also showed a correlation with our ceRNAs.…”