Gene Model Related to m6A Predicts the Prognostic Effect of Immune Infiltration on Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson’s correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

Download Full-text

Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211045823 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110458

Author(s):

Jing Sun ◽

Guiqing Fang ◽

Zhibin Zuo ◽

Xijiao Yu ◽

Lande Xue ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

The Relationship

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC

Download Full-text

Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma

Annals of Oncology ◽

10.1093/annonc/mdy507 ◽

2019 ◽

Vol 30 (1) ◽

pp. 57-67 ◽

Cited By ~ 28

Author(s):

M. Oliva ◽

A. Spreafico ◽

M. Taberna ◽

L. Alemany ◽

B. Coburn ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Neck Squamous Cell Carcinoma ◽

Immune Biomarkers

Download Full-text

A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

BMC Cancer ◽

10.1186/s12885-021-08765-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Congyu Shi ◽

Shan Liu ◽

Xudong Tian ◽

Xiaoyi Wang ◽

Pan Gao

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Risk Group ◽

High Risk Group ◽

Mutation Model ◽

Therapeutic Responses

Abstract Background Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC. Methods Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model. Results TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies. Conclusion The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.

Download Full-text

The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.688545 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guanying Feng ◽

Feifei Xue ◽

Yingzheng He ◽

Tianxiao Wang ◽

Hua Yuan

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Network Analysis ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Potential Biomarker ◽

Score Model

ObjectivesThis study aimed to identify genes regulating cancer stemness of head and neck squamous cell carcinoma (HNSCC) and evaluate the ability of these genes to predict clinical outcomes.Materials and MethodsThe stemness index (mRNAsi) was obtained using a one-class logistic regression machine learning algorithm based on sequencing data of HNSCC patients. Stemness-related genes were identified by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis (LASSO). The coefficient of LASSO was applied to construct a diagnostic risk score model. The Cancer Genome Atlas database, the Gene Expression Omnibus database, Oncomine database and the Human Protein Atlas database were used to validate the expression of key genes. Interaction network analysis was performed using String database and DisNor database. The Connectivity Map database was used to screen potential compounds. The expressions of stemness-related genes were validated using quantitative real‐time polymerase chain reaction (qRT‐PCR).ResultsTTK, KIF14, KIF18A and DLGAP5 were identified. Stemness-related genes were upregulated in HNSCC samples. The risk score model had a significant predictive ability. CDK inhibitor was the top hit of potential compounds.ConclusionStemness-related gene expression profiles may be a potential biomarker for HNSCC.

Download Full-text

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽

10.3390/medicina57111151 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1151

Author(s):

Shinsuke Suzuki ◽

Satoshi Toyoma ◽

Yohei Kawasaki ◽

Koh Koizumi ◽

Nobuko Iikawa ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Neck Squamous Cell Carcinoma ◽

Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Download Full-text