A Ferroptosis-Related Prognostic Signature Based on Antitumor Immunity and Tumor Protein p53 Mutation Exploration for Guiding Treatment in Patients With Head and Neck Squamous Cell Carcinoma

Background: Due to the lack of accurate guidance of biomarkers, the treatment of head and neck squamous cell carcinoma (HNSCC) has not been ideal. Ferroptosis plays an important role in tumor suppression and treatment of patients. However, tumor protein p53 (TP53) mutation may promote tumor progression through ferroptosis. Therefore, it is particularly important to mine prognostic-related differentially expressed ferroptosis-related genes (PR-DE-FRGs) in HNSCC to construct a prognostic model for accurately guiding clinical treatment.Methods: First, the HNSCC data obtained from The Cancer Genome Atlas (TCGA) was used to identify PR-DE-FRGs for screening candidate genes to construct a prognostic model. We not only used a variety of methods to verify the accuracy of the model for predicting prognosis but also explored the role of ferroptosis in the development of HNSCC from the perspective of the immune microenvironment and mutation. Finally, we explored the correlation between the prognostic model and clinical treatment and drew a high-precision nomogram to predict the prognosis.Results: Seventeen of the 29 PR-DE-FRGs were selected to construct a prognostic model with good predictive performance. Patients in the low-risk group were found to have a greater number of CD8 + T cells, follicular helper T cells, regulatory T cells, mast cells, T-cell costimulations, and type II interferon responses. A higher tumor mutation burden (TMB) was observed in the low-risk group and was associated with a better prognosis. A higher risk score was found in the TP53 mutation group and was associated with a worse prognosis. The risk score is closely related to the expression of immune checkpoint inhibitors (ICIs)-related genes such as PD-L1 and the IC50 of six chemotherapeutic drugs. The nomogram we constructed performs well in predicting prognosis.Conclusion: Ferroptosis may participate in the progression of HNSCC through the immune microenvironment and TP53 mutation. The model we built can be used as an effective predictor of immunotherapy and chemotherapy effects and prognosis of HNSCC patients.

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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.

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

Journal of Oncology ◽

10.1155/2021/1814266 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yaping Deng ◽

Kehua Li ◽

Fengwu Tan ◽

Hanbo Liu

Keyword(s):

Immune Response ◽

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Immune Checkpoint ◽

Neck Squamous Cell Carcinoma ◽

Immune Microenvironment

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.

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An Immune Feature-Based, Three-Gene Scoring System for Prognostic Prediction of Head-and-Neck Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.739182 ◽

2022 ◽

Vol 11 ◽

Author(s):

Yamin Zhang ◽

Xiayan Luo ◽

Jing Yu ◽

Kejia Qian ◽

Huiyong Zhu

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Candidate Genes ◽

Risk Score ◽

Squamous Cell ◽

Scoring System ◽

Cox Regression ◽

Neck Squamous Cell Carcinoma

Head-and-neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of neck lymph node metastasis (LNM), a key prognostic factor. Therefore, identifying the biological processes during LNM of HNSCC has significant clinical implications for risk stratification. This study performed Gene Ontology enrichment analysis of differentially expressed genes between tumors with LNM and those without LNM and identified the involvement of immune response in the lymphatic metastasis of HNSCC. We further identified greater infiltrations of CD8+ T cells in tumors than in adjacent normal tissues through immunochemistry in the patient cohort (n = 62), indicating the involvement of CD8+ T cells in the antitumor immunity. Hierarchical clustering analysis was conducted to initially identify the candidate genes relevant to lymphocyte-mediated antitumor response. The candidate genes were applied to construct a LASSO Cox regression analysis model. Three genes were eventually screened out as progression‐related differentially expressed candidates in HNSCC and a risk scoring system was established based on LASSO Cox regression model to predict the outcome in patients with HNSCC. The score was calculated using the formula: 0.0636 × CXCL11 − 0.4619 × CXCR3 + 0.2398 × CCR5. Patients with high scores had significantly worse overall survival than those with low scores (p < 0.001). The risk score showed good performance in characterizing tumor-infiltrating lymphocytes and provided a theoretical basis for stratifying patients receiving immune therapies. Additionally, a nomogram including the risk score, age, and TNM stage was constructed. The prediction model displayed marginally better discrimination ability and higher agreement in predicting the survival of patients with HNSCC compared with the TNM stage.

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The Potential of Oxidative Stress Related Genes as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207325666211207154436 ◽

2021 ◽

Vol 25 ◽

Author(s):

Xin Wang ◽

Gang Zhou

Keyword(s):

Oxidative Stress ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Risk Model ◽

Risk Group ◽

Enrichment Analysis ◽

Cox Analysis

Background: The occurrence of oxidative stress is an important hallmark of tumorigenesis and the development of cancers, including head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to identify a robust oxidative stress-related prognostic model in HNSCC. Methods: Oxidative stress genes related to the prognosis of HNSCC were identified through multiple bioinformatics methods. Results: The expression profile of differential genes related to oxidative stress and functional enrichment analysis were obtained from the HNSCC cohort of The Cancer Genome Atlas (TCGA-HNSC). Then, the HNSCC prognostic risk model was constructed of thirteen screened genes through univariate Cox analysis, the least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox analysis. Kaplan–Meier curve indicated that the low-risk group had a better survival outcome than the high-risk group. The clinical utility of the risk model was validated in the GSE41613 dataset. The risk score was an independent prognostic indicator in the training and validation sets. In addition, the risk score was in a positive correlation with tumor stage, lymph node infiltration, and the status of the primary site. Gene set enrichment analysis (GSEA) illustrated that many biological processes associated with immunity were significantly enriched in the low-risk group of the training cohort. Conclusion:: The oxidative stress-related risk signature was a promising predictor for the prognosis of HNSCC patients, which might assist in making individualized therapy programs.

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Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma

Disease Markers ◽

10.1155/2020/8899337 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Cheng Li ◽

Zeng-hong Wu ◽

Kun Yuan

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Risk Group ◽

Neck Squamous Cell Carcinoma ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Kaplan Meier

Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in the world, with low survival and poor quality of life. Autophagy-associated genes (ATGs) have been reported to be involved in the initiation and progression of malignancies. Here, we aimed to investigate the association between autophagy-associated genes and the outcomes in HNSCC patients. Methods. We obtained ATGs with prognostic values by analyzing the datasets from The Cancer Genome Atlas (TCGA) and Human Autophagy Database (HADb). The enrichment functions of autophagy differential genes were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Kaplan-Meier method was applied to the survival curve analysis. A prognostic autophagy-related gene signature was established, and its independence was verified. Results. We acquired a total of 529 samples and 232 ATGs; further, we identified 45 genes associated with prognosis and built a prognosis autophagy signature based on risk score of 15 genes. Patients were divided into two groups based on risk scores. The Kaplan-Meier curve illustrated that the survival rate of the high-risk group was significantly lower than that of the low-risk group in both the training group and validation group. The ROC curve revealed that the risk score had the highest AUC value in the 3rd and 5th years, reaching 0.703 and 0.724, which are higher than other risk factors such as gender, age, and TNM stage. The nomogram further confirmed its weight in the prognosis of HNSCC patients. Through KEGG and GO enrichment analyses, we observed that ATGs were involved in the tumorigenesis and invasion of tumor by various mediating pathways. We gained 3 hub genes (MAP1LC3B, FADD, and LAMP1) and further analyzed the survival curves, mutations, differential expressions, and their roles in tumors on the online websites. Conclusion. We identified a novel autophagy-related signature that may provide promising biomarker genes for the treatment and prognosis of HNSCC. We need to validate its prognostic value by applying it to the clinic.

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Development and Validation of a Hypoxia-Related Gene Pairs Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

10.21203/rs.3.rs-77415/v1 ◽

2020 ◽

Author(s):

Zhao Ding ◽

Hefeng Li ◽

Deshun Yu

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

High Risk ◽

Gene Silencing ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Poor Prognosis ◽

Risk Group ◽

Low Risk

Abstract Objective Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.Methods Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.Results A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, and T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, and T cells CD8, etc. were significantly higher in the low-risk group.Conclusion In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

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Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-002088 ◽

2021 ◽

Vol 9 (5) ◽

pp. e002088

Author(s):

Dan P Zandberg ◽

Ashley V Menk ◽

Maria Velez ◽

Daniel Normolle ◽

Kristin DePeaux ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cd8 T Cells ◽

Oxidative Metabolism ◽

Cox Regression ◽

Tumor Hypoxia ◽

Parental Line

The majority of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC) (R/M) do not benefit from anti-PD-1 therapy. Hypoxia induced immunosuppression may be a barrier to immunotherapy. Therefore, we examined the metabolic effect of anti-PD-1 therapy in a murine MEER HNSCC model as well as intratumoral hypoxia in R/M patients. In order to characterize the tumor microenvironment in PD-1 resistance, a MEER cell line was created from the parental line that are completely resistant to anti-PD-1. These cell lines were then metabolically profiled using seahorse technology and injected into C57/BL6 mice. After tumor growth, mice were pulsed with pimonidazole and immunofluorescent imaging was performed to analyze hypoxia and T cell infiltration. To validate the preclinical results, we analyzed tissues from R/M patients (n=36) treated with anti-PD-1 mAb, via immunofluorescent imaging for number of CD8+ T cells (CD8), Tregs and the percent area (CAIX) and mean intensity (I) of carbonic anhydrase IX in tumor. We analyzed disease control rate (DCR), progression free survival (PFS), and overall survival (OS) using proportional odds and proportional hazards (Cox) regression. We found that anti-PD-1 resistant MEER has significantly higher oxidative metabolism, while there was no difference in glycolytic metabolism. Intratumoral hypoxia was significantly increased and CD8+ T cells decreased in anti-PD-1 resistant tumors compared with parental tumors in the same mouse. In R/M patients, lower tumor hypoxia by CAIX/I was significantly associated with DCR (p=0.007), PFS, and OS, and independently associated with response (p=0.028) and PFS (p=0.04) in a multivariate model including other significant immune factors. During PD-1 resistance, tumor cells developed increased oxidative metabolism leading to increased intratumoral hypoxia and a decrease in CD8+ T cells. Lower tumor hypoxia was independently associated with increased efficacy of anti-PD-1 therapy in patients with R/M HNSCC. To our knowledge this is the first analysis of the effect of hypoxia in this patient population and highlights its importance not only as a predictive biomarker but also as a potential target for therapeutic intervention.

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Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-018-5223-x ◽

2018 ◽

Vol 276 (2) ◽

pp. 521-533 ◽

Cited By ~ 2

Author(s):

Chanatip Metheetrairut ◽

Chanticha Chotigavanich ◽

Kanchana Amornpichetkul ◽

Phawin Keskool ◽

Sunun Ongard ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

Neck Squamous Cell Carcinoma ◽

Mutation Status ◽

Expression Levels

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903 Human cancer-associated fibroblast subsets can predict immune checkpoint response in head and neck cancer patients

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.903 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A947-A947

Author(s):

Diana Graves ◽

Aleksandar Obradovic ◽

Michael Korrer ◽

Yu Wang ◽

Sohini Roy ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Head And Neck Cancer ◽

Cell Carcinoma ◽

Head And Neck ◽

Single Cell ◽

Rna Sequencing ◽

Neck Cancer ◽

Squamous Cell ◽

Single Cell Rna Sequencing

BackgroundUse of anti-PD-1 immune checkpoint inhibitors (ICI) is currently the first line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but critical work remains in identifying factors guiding resistance mechanisms.1 2 While recent studies have specifically implicated cancer-associated fibroblasts (CAFs) as potential mediators of immunotherapy response, the immunoregulatory role of CAFs in head and neck cancer has not been thoroughly explored.3–5MethodsTo determine if there are changes in cell populations associated with anti-PD-1 therapy in head and neck cancer patients, we performed high dimensional single-cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the anti-PD-1 therapy, nivolumab, for the duration of one month. Tumor specimens were analyzed pre- and post-treatment with single-cell RNA sequencing performed on 4 patients as well as bulk RNA sequencing on 40 patients. Matched scRNA-SEQ data was analyzed using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform to determine TME cells that correlated with response and resistance to nivolumab.6 For CAF functional studies, surgical tumor specimens were processed and enriched for CAF subtypes, and these were co-cultured with T cells from peripheral blood and tumor infiltrating lymphocytes.ResultsWe identified 14 distinct cell types present in HNSCC patients. Of these 14 cell types, the fibroblast subtype showed significant changes in abundance following nivolumab treatment. We identified 5 distinct clusters of cancer-associated fibroblast subsets (HNCAF-0, 1, 2, 3, and 4) of which, two clusters, HNCAF-0 and HNCAF-3 were predictive of patient response to anti-PD-1 therapy. To determine the significance of these CAF subsets’ function, we isolated HNCAF-0/3 cells from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that HNCAF-0/3 reduced TGFβ-dependent PD-1+TIM-3+ exhaustion of T cells and increased CD103+NKG2A+ resident memory phenotype and cytotoxicity to enhance overall function.ConclusionsTo our knowledge, we are the first to characterize CAF heterogeneity within the head and neck TME and show direct immunostimulatory activity of CAFs. Our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC, and we have identified clinically actionable CAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.Trial RegistrationNCT03238365ReferencesFerris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–1867.Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–965.Dominguez CX, Muller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov 2020;10:232–253.Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20212–20217.Kieffer Y, Hocine HR, Gentric G, Pelon F, Bernard C, Bourachot B, Lameiras S, Albergante L, Bonneau C, Guyard A, et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov 2020;10:1330–1351.Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH, Rathmell WK, Jonasch E, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 2021;184:2988–3005.Ethics ApprovalPatients provided informed consent for this work. All experimental procedures were approved by the Institutional Review Board of Vanderbilt University Medical Center (IRB: 171883).

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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.

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