Prognosis Of Head And Neck Squamous Cell Carcinoma Research Articles

Association between cancer stem cell gene expression signatures and prognosis in head and neck squamous cell carcinoma

BackgroundVarious cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts.MethodsTo predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1).ResultsPatients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (–) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy.ConclusionThe CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (–) status who were classified in more detail.

A multifaceted and feasible prognostic model of amino acid metabolism-related genes in the immune response and tumor microenvironment of head and neck squamous cell carcinomas.

We investigated the role of amino acid metabolism (AAM) in head and neck squamous cell carcinoma (HNSCC) tissues to explore its prognostic value and potential therapeutic strategies. A risk score based on four AAM-related genes (AMG) was constructed that could predict the prognosis of HNSCC. These four genes were up-regulated in HNSCC tissues and might act as oncogenes. Internal validation in The Cancer Genome Atlas (TCGA) by bootstrapping showed that patients with high-risk scores had a poorer prognosis than patients with low-risk scores, and this was confirmed in the Gene Expression Omnibus (GEO) cohort. There were also differences between the high-risk and low-risk groups in clinical information and different anatomical sites such as age, sex, TNM stage, grade stage, surgery or no surgery, chemotherapy, radiotherapy, no radiotherapy, neck lymph node dissection or not, and neck lymphovascular invasion, larynx, overlapping lesion of lip, and oral cavity and pharynx tonsil of overall survival (OS). Immune-related characteristics, tumor microenvironment (TME) characteristics, and immunotherapy response were significantly different between high- and low-risk groups. The four AMGs were also found to be associated with the expression of markers of various immune cell subpopulations. Therefore, our comprehensive approach revealed the characterization of AAM in HNSCC to predict prognosis and guide clinical therapy.

Exploration of a predictive model based on genes associated with fatty acid metabolism and clinical treatment for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumors of the head and neck and presents high risks of recurrence and poor prognosis postoperatively. The aim of this study was to establish a predictive model based on fatty acid metabolism (FAM) genes to forecast the prognosis of HNSCC patients and the subsequent treatment strategies. We accessed the TCGA and GEO databases for HNSCC genes and clinical data. The FAM risk score model was created and validated using a combination of univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Combining risk scores and clinical characteristics, a nomogram was established and assessed. Subsequently, the function, gene mutation, immune difference, and chemotherapeutic drug sensitivity of the groups with high- and low-risk scores were analyzed. Consequently, the mode's validity was evaluated comprehensively by combining single gene analysis. The FAM risk score model for predicting HNSCC prognosis had certain validity. Patients in the high- and low-risk groups had genetic mutations, and the prognosis was the poorest for the high-risk groups with high genetic mutations. The patients with low-risk scores were suitable for immunotherapy since they had increased infiltration of immune cells. In contrast, the patients in the other groups were more suitable for chemotherapy. The results of this study demonstrated that the FAM risk score model may predict the prognosis of HSNCC and has a certain therapeutic guidance value.

M6A RNA methylation regulator-related signatures exhibit good prognosis prediction ability for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) has become the sixth most common malignant disease worldwide and is associated with high mortality, with an overall 5-year survival rate of less than 50%. Recent studies have demonstrated that aberrantly expressed m6A regulators are involved in multiple biological and pathological processes, including cancers, but the specific mechanisms of m6A regulators in HNSCC are not well elucidated. In this study, we adopted The Cancer Genome Atlas (TCGA)-HNSCC database and performed a consensus clustering analysis to classify the HNSCC samples. Least absolute shrinkage and selection operator (LASSO) regression was applied to construct an m6A signature-based HNSCC risk prediction model. Cell type identification based on estimating relative subsets of RNA transcripts (CIBERSORT) algorithms was adopted to evaluate the immune cell infiltration level in the tumor microenvironment. Based on the expression of m6A regulators in HNSCC, we identified two clusters, cluster 1 (C1) and cluster 2 (C2). C2 showed a better prognosis than C1 and was mainly enriched in the HIPPO, MYC, NOTCH, and NRF signaling pathways. We constructed an m6A signature-based risk score model and classified patients into high- and low-risk score subgroups. The high-risk-score group showed poor clinical characteristics, higher immune infiltration levels, higher chemokine and chemokine receptor expression levels, and lower immune checkpoint gene expression than the low-risk-score subgroup. In conclusion, our comprehensive analysis suggests that the m6A signature-based risk score might function as a good prognostic predictor. Our study may provide novel therapeutic clues and help predict the prognosis of HNSCC.

A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and patients with HNSCC possess early metastases and poor prognosis. Systematic therapies (including chemotherapy, targeted therapy, and immunotherapy) are generally applied in the advanced/late stages of HNSCC, but primary and acquired resistance eventually occurs. At present, reliable biomarkers to predict the prognosis of HNSCC have not been completely identified. Recent studies have shown that neutrophil extracellular traps (NETs) are implicated in cancer progression, metastasis and cancer immune response, and NET-related gene signatures are associated with the prognosis of patients with several human cancers. To explore whether NET-related genes play crucial roles in HNSCC, we have performed systematic analysis and reported several findings in the current study. Firstly, we identified seven novel NET-related genes and developed a NET-score signature, which was highly associated with the clinicopathological and immune traits of the HNSCC patients. Then, we, for the first time, found that NIFK was significantly upregulated in HNSCC patient samples, and its levels were significantly linked to tumor malignancy and immune status. Moreover, functional experiments confirmed that NIFK was required for HNSCC cell proliferation and metastasis. Altogether, this study has identified a novel NET-score signature based on seven novel NET-related genes to predict the prognosis of HNSCC and NIFK has also explored a new method for personalized chemo-/immuno-therapy of HNSCC.

FN1 promotes prognosis and radioresistance in head and neck squamous cell carcinoma: From radioresistant HNSCC cell line to integrated bioinformatics methods.

Background: Radioresistance in head and neck squamous cell carcinoma (HNSCC) patients means response failure to current treatment. In order to screen radioresistant biomarkers and mechanisms associated with HNSCC, differentially expressed genes (DEGs) associated with radioresistance in HNSCC were investigated. Methods: The HNSCC cell line with radioresistance, Hep2-R, was established and detected the radiosensitivity using MTT, colony formation assay and flow cytometry analysis. Clariom™ D chip was applied to compare DEGs between Hep2 and Hep2-R groups and build the differential gene expression profiles associated with radioresistance in HNSCC. Bioinformatic analysis were used to find biological functions and pathways that related to radioresistance in HNSCC, including cell adhesion, cytochrome P450 and drug metabolism. Gene Expression Omnibus (GEO) datasets were selected to verify DEGs between HNSCC radioresistant cells and tissues. The representation of DEGs were validated between HNSCC patients with complete response and post-operative radiation therapy failure. In addition, we evaluated the clinical prognosis of DEGs using The Cancer Genome Atlas (TCGA) database. Results: 2,360 DEGs (|Fold Change|>1.5, p < 0.05) were identified between Hep2 and Hep2-R, including 1,144 upregulated DEGs and 1,216 downregulated DEGs. They were further verified by HNSCC radioresistant cells and tissues in GEO. 13 radioresistant DEGs showed same difference in expression level between cells and tissues. By comparing 13 DEGs with HNSCC patients, upregulations of FN1, SOX4 and ETV5 were found identical with above results. Only FN1 was a prognostic indicator of HNSCC in TCGA. Conclusion: FN1 is the potential novel biomarker for predicting poor prognosis and radioresistance in HNSCC patients. Overexpression of FN1 plays an important role in the tumorigenesis, prognosis and radioresistance of HNSCC.

The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma.

Background: The PITX gene family, comprising PITX1, PITX2, and PITX3, is critical in organogenesis and has been evolutionary conserved in animals. PITX genes are associated with the advanced progression and poor prognosis of multiple cancers. However, the relationship between the PITX genes and head and neck squamous cell carcinoma (HNSC) has not been reported. Methods: We used data from The Cancer Genome Atlas (TCGA) to analyze the association between PITX mRNA expression and clinicopathological parameters of patients with HNSC. The prognostic value of PITX genes was evaluated using the Kaplan-Meier plotter. Multivariate Cox analysis was used to screen out prognosis-associated genes to identify better prognostic indicators. The potential roles of PITX1 and PITX2 in HNSC prognosis were investigated using the protein-protein interaction (PPI) network, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The correlation between PITX1 and PITX2 expression or methylation and immune cell infiltration was evaluated using the tumor-immune system interaction database (TISIDB). MethSurv was used to identify DNA methylation and its effect on HNSC prognosis. Results: PITX genes expression was correlated with different cancers. PITX1 and PITX2 expression was lower in the patients with HNSC. In HNSC, PITX1 expression was significantly related to the clinical stage, histologic grade, and N stage, while PITX2 expression was only significantly related to the histologic grade. The high expression of PITX3 was significantly related to the histologic grade, T stage, and N stage. Survival analysis revealed that PITX genes had prognostic value in HNSC, which was supported by multivariate Cox analysis. PPI network and enrichment analysis showed that the genes interacting with PITX1 and PITX2 belonged predominantly to signaling pathways associated with DNA binding and transcription. Of the CpG DNA methylation sites in PITX1 and PITX2, 28 and 22 were related to the prognosis of HNSC, respectively. Additionally, PITX1 and PITX2 expression and methylation was associated with tumor-infiltrating lymphocytes (TILs). Conclusion: The PITX genes were differentially expressed in patients with HNSC, highlighting their essential role in DNA methylation and tumor-infiltrating immune cell regulation, as well as overall prognostic value in HNSC.

Prognostic signature of endoplasmic reticulum stress-related long noncoding RNAs in head and neck squamous cell carcinoma: Association with somatic mutation and tumor immune microenvironment

Background/purposeAnalysis of endoplasmic reticulum stress (ERS)-related long noncoding RNAs (LncRNAs) may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to comprehensively analyze the ERS-related LncRNAs signature and its effects on the prognosis, tumorigenesis, and tumor immune microenvironment in HNSCC. Materials and methodsThe transcriptome data of HNSCC were obtained from TCGA. Least absolute shrinkage selection operator algorithm, and multivariate Cox regression were used to screen LncRNAs for the signature construction. Somatic mutation, gene enrichment, and immune infiltration analyses were further performed. Results458 ERS-related LncRNAs were identified and 55 of which were correlated with HNSCC prognosis. Ten ERS-related LncRNAs were selected to establish a risk prediction signature. When dividing patients into high-risk and low-risk groups by signature score, high-risk group correlated with worse survival rates (hazard ratio = 1.211; 95% confidence interval 1.123–1.306, P < 0.001). The area under the curve was 0.751 and 0.716 in the training and validation cohorts at 3-year. Moreover, high-risk group have increased somatic mutation rates and reduced infiltration abundancy of B cells and CD8+ T cells. ConclusionThe prognostic signature based on ERS-related LncRNAs may serve as a predictor of altered oncogene mutations and immune microenvironment, which provided an insight into the relationship between ERS, LncRNAs, and tumor progression.

Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Background SLC2A3 is upregulated in various cancer types and promotes proliferation, invasion, and metabolism. However, its role in the prognosis and immune regulation of head and neck squamous cell carcinoma (HNSCC) is still obscure. This study is aimed at exploring the prognostic and immunotherapeutic potential of SLC2A3 in HNSCC. Methods All data were downloaded from TCGA database and integrated via R software. SLC2A3 expression was evaluated using R software, TIMER, CPTAC, and HPA databases. The association between SLC2A3 expression and clinicopathologic characteristics was assessed by R software. The effect of SLC2A3 on survival was analyzed by R software and Kaplan-Meier Plotter. Genomic alterations in SLC2A3 were investigated using the cBioPortal database. Coexpression of SLC2A3 was studied using LinkedOmics and STRING, and enrichment analyses were performed with R software. The relationship between SLC2A3 expression and immune infiltration was determined using TIMER and TISIDB databases. Immune checkpoints and ESTIMATE score were analyzed via the SangerBox database. Results SLC2A3 expression was upregulated in HNSCC tissues compared to normal tissues. It was significantly related to TNM stage, histological grade, and alcohol history. High SLC2A3 expression was associated with poor prognosis in HNSCC. Coexpression analysis indicated that SLC2A3 mostly participated in the HIF-1 signaling pathway and glycolysis. Furthermore, SLC2A3 expression strongly correlated with tumor-infiltrating lymphocytes in HNSCC. Conclusion SLC2A3 could serve as a potential prognostic biomarker for tumor immune infiltration in HNSCC.

Multiomics Integrative Analysis Identifying EPC1 as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

Background Biomarker research in head and neck squamous cell carcinoma (HNSCC) is constantly revealing promising findings. An enhancer of polycomb homolog 1 (EPC1) was found to play a procancer role in nasopharyngeal carcinoma (NPC), but its role in HNSCC with strong heterogeneity is still unclear. Herein, we investigated the prognostic significance and related mechanisms of EPC1 in HNSCC. Methods The Kaplan-Meier plotter was used to evaluate the prognostic significance of EPC1. Based on a range of published public databases, the multiomics expression of EPC1 in HNSCC was explored to investigate the mechanisms affecting prognosis. Results According to the clinical data, high EPC1 expression in HNSCC was a predictor of patient prognosis (hazard ratio (HR) = 0.64; 95% confidence interval (CI) 0.49-0.83; P < 0.01). EPC1 expression varied among clinical subtypes and was related to key factors, such as TP53 and human papillomavirus (HPV) (P < 0.05). At the genetic level, EPC1 expression level may be associated with protein phosphorylation, cell adhesion, cancer-related pathways, etc. For the noncoding region, a competing endogenous RNA network was constructed, and 6 microRNAs and 12 long noncoding RNAs were identified. At the protein level, a protein-protein interaction (PPI) network related to EPC1 expression was constructed and found to be involved in HPV infection, endocrine resistance, and multiple cancer pathways. At the immune level, EPC1 expression was correlated with a variety of immune cells and immune molecules, which together constituted the immune microenvironments of tumors. Conclusion High EPC1 expression may predict a better prognosis in HNSCC, as it is more frequently found in HNSCC with HPV infection. EPC1 may participate in the genomics, transcriptomics, proteomics, and immunomics of HNSCC, and the results can provide a reference for the development of targeted drugs and evaluation of patient prognosis.

RNA 5-Methylcytosine Regulator NSUN3 promotes tumor progression through regulating immune infiltration in head andneck squamous cell carcinoma.

This study aimed to determine whether the RNA, 5-methylcytosine (m5C), is involved in the progression of head and neck squamous cell carcinoma (HNSCC). We used least absolute shrinkage and selection operator to establish a prognostic score (PS) model based on the m5C regulator expression. Immune scores were calculated using the estimation of stromal and immune cells in malignant tumor tissues using expression data. The biological functions of the m5C regulator, NOP2/Sun RNA methyltransferase 3 (NSUN3), were thoroughly investigated in vitro and in vivo. The PS model acted as efficient prognostic factors in HNSCC. The expression of NSUN3, with the maximum weight, was found to be upregulated and indicated a poor prognosis. Meanwhile, NSUN3 knockdown inhibited the tumor proliferation and growth both in vitro and in vivo. High PS status was negatively correlated with CD8+ T, γδ+ T, and M1 macrophage percentages. NSUN3 knockdown increased the infiltration of M1 macrophages but decreased the percentage of M2 macrophages. The PS index is a novel and promising biomarker for predicting the prognosis and immune infiltration microenvironment in HNSCC. Moreover, NSUN3 plays a key role in this process and may serve as a potential therapeutic target for HNSCC.

Identification of RNA Modification-Associated Alternative Splicing Signature as an Independent Factor in Head and Neck Squamous Cell Carcinoma

Objective Head and neck squamous cell carcinoma (HNSCC) is a highly heterotopic malignant tumor. Alternative splicing (AS) and RNA modification have been reported to be involved in tumorigenesis. Therefore, we constructed RNA modification-associated AS (RMA-AS) signature model to predict the prognosis of HNSCC. Methods AS events and RNA-modified gene expression information were downloaded from TCGA-HNSCC database. Univariate Cox regression analysis was employed for analyzing prognosis-related AS events. RMA-AS events were obtained by constructing a coexpression network between RNA modification-associated genes and AS events using WGCNA package. The prognostic signatures were analyzed by LASSO, univariate Cox, and multivariate Cox regression. Kaplan-Meier survival analysis, proportional hazard model, and ROC curve were performed to verify the prognostic value. “ESTIMATE” R package, ssGSEA algorithm, and CIBERSORT method were used to detect immune microenvironment in HNSCC. Cytoscape was utilized to build a regulatory network of splicing factor-regulated RMA-AS. Results There were 16,574 prognostic AS events and 4 differentially expressed RNA modification-associated genes in HNSCC. Based on RMA-AS events, we obtained a risk model consisting of 14 AS events, named RMA-AS_Score. The samples were divided into RMA-AS_Score high- and RMA-AS_Score low-risk groups, according to the risk score. The RMA-AS_Score high group was related to poor prognosis. Moreover, the RMA-AS_Score signature was an independent prognostic predictor and was related to tumor grade. Meanwhile, the AUC value of RMA-AS_Score was 0.652, which is better than other clinical characteristics. Besides, a nomogram prediction model of quantitative prognosis has also been developed, which has robust effectiveness in predicting prognosis. In addition, the prognostic signature was observably related to immune microenvironment and immune checkpoint. Finally, 14 splicing factors were identified and constructed into a network of splicing factor-regulated RMA-AS. Conclusion We identified the RMA-AS signature of HNSCC. This signature could be treated as an independent prognostic predictor.

Predicting the Immune Microenvironment and Prognosis with a NETosis-Related lncRNA Signature in Head and Neck Squamous Cell Carcinoma.

Background The mechanistic aspects of the involvement of long noncoding RNAs (lncRNAs) in NETosis, the process of neutrophil extracellular trap (NET) formation in head and neck squamous cell carcinoma (HNSCC), lack comprehensive elucidation. The involvement of these molecules in the immune microenvironment and plausible HNSCC prognosis remain to see the light of the day. The plausible functioning of NETosis-related lncRNAs with their plausible prognostic impact in HNSCC was probed in this work. Methods The scrutiny of lncRNAs linked to NETosis entailed the probing of twenty-four genes associated with the process employing Pearson's correlation analysis on HNSCC patients' RNA sequencing data from The Cancer Genome Atlas (TCGA) database. The application of univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses yielded a NETosis-related lncRNA signature that was subjected to probing for its suitability in prognosis employing survival and nomogram analyses. Results The NETosis-related lncRNA signature inclusive of five lncRNAs facilitated patients to be segregated as high-risk and low-risk groups with the former documenting a poor prognosis. Regression unearthed that the risk score was an independent factor for prognosis. The receiver operating characteristic (ROC) or receiver operating characteristic curve analysis documented a one-year area under time-dependent ROC curve (AUC) value of 0.711 that is corroborative of the accuracy of this signature. Additional probing documented an evident enriching of immune-linked pathways in the low-risk patients, while the high-risk patients documented an immunologically “cold” profile as per the infiltration of immune cells. We verified lncRNA expression from our NETosis-related lncRNA signature in vitro, which reflects the reliability of our model to a certain extent. Moreover, we also verified the function of the lncRNA. We found that LINC00426 contributes to the innate immune cGAS-STING signaling pathway, which explain to some extent the role of our prognostic model in predicting “hot” and “cold” tumors. Conclusions The plausible prognostic relevance of the NETosis-related lncRNA signature (with five lncRNAs) emerges that is suggestive of its promise in targeting HNSCC.

The Prognostic Role of Cuproptosis in Head and Neck Squamous Cell Carcinoma Patients: A Comprehensive Analysis.

Purpose Head and neck squamous cell carcinoma (HNSCC) exhibits a high mortality and morbidity rate, and its treatment is facing clinical challenges. Cuproptosis, a copper-dependent cell death process, can help derive new forms of cancer therapies. However, the potential of cuproptosis-related genes (CRGs) as novel biomarkers for risk prediction, screening, and prognosis remains to be further explained in HNSCC. Methods We built a prognostic multigene signature with CRGs, which is associated with the tumor immune microenvironment (TME) by gene set enrichment analysis (GSEA), in the TCGA cohort. Furthermore, we systematically correlated risk signature with immunological characteristics in TME including tumor-infiltrating immune cells (TIICs), immune checkpoints, T cell inflamed score, and cancer immunity cycles. We also thoroughly investigated the biological functions of cuproptosis-associated lncRNAs and its immunological characteristics. Results CRGs-related prognostic model showed good prediction performance. A higher risk score was associated with a poorer overall survival (OS) than those with low-risk scores, according to the results of the survival analysis (p < 0.0001). The risk score was significantly related to the variable clinicopathological factors. Samples with high-risk scores had lower levels of CD8+ T cells infiltration. Immune therapy might be effective for the low-risk subtype of HNSCC patients (p < 0.05). Moreover, 11 differentially expressed lncRNAs as the independent prognostic factor could also predict TME in an accurate manner. Conclusion Our study identified and validated novel cuproptosis-related biomarkers for HNSCC prognosis and screening, which offer better insights into developing accurate, reliable, and novel cancer therapies in the era of precision medicine.

Prognostic value of CD247 in patients with head and neck squamous cell carcinoma: bioinformatic analysis of TCGA database.

BackgroundHead and neck squamous cell carcinoma (HNSC) is the 7th most common type of cancer in the world. Through the advantages of The Cancer Genome Atlas (TCGA) large-scale sequencing-based genome analysis technology, we can explore the potential molecular mechanisms that can improve the prognosis of HNSC patients.MethodsThe HNSC transcriptome and clinical data were downloaded from TCGA database. A univariate survival analysis and differential expression analysis were conducted to obtain the intersection gene set. A protein-protein interaction (PPI) analysis, modular analysis, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were then conducted to identify the hub genes. Clinical correlation analysis, univariate and multivariate Cox regression analyses were performed on the identified hub genes to determine the prognostic impact of hub genes on HNSC patients.ResultsIn total, 601 intersecting gene sets were obtained. A modular analysis was conducted, and the highest scoring module was 19.304. Based on the GO/KEGG enrichment analysis results, CD247 molecule (CD247) was ultimately selected as the gene for this study. The CD247 were divided into a high-expression group and a low-expression group. The Kaplan-Meier survival curve analysis showed that there was a significant difference between the 2 groups (P<0.0001). The median survival time of the low-expression CD247 group was 30.9 months, and the 5-year survival rate was 36.4%. While the median survival time of the high-expression CD247 group was 68.8 months, and the 5-year survival rate was 52.3%. The clinical correlation analysis showed that CD247 was significantly negatively correlated with pathological tumor stage (pT) and pathological nodal extracapsular spread. Gene Set Enrichment Analysis (GSEA) showed that CD247 activating KEGG pathway hsa04650 and hsa04660.ConclusionsCD247 is an independent protective factor in the prognosis of HNSC patients. By activating the hsa04650 and hsa04660 pathways, the expression of interferon gamma, interleukin (IL)-2, and IL-10 is promoted, which in turn improves the tumor immune monitoring ability of the body, induces tumor cell apoptosis, and inhibits tumor cell growth. CD247 is a potential target for improving the clinical treatment effect of HNSC and the prognosis of patients.

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

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. Oxidative stress genes related to the prognosis of HNSCC were identified through multiple bioinformatics methods. 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 (TCGAHNSC). 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. The oxidative stress-related risk signature was a promising predictor for the prognosis of HNSCC patients, which might assist in making individualized therapy programs.

Identification and validation of the role of c-Myc in head and neck squamous cell carcinoma.

BackgroundMany studies have shown that c-Myc plays a critical role in tumorigenesis. However, the molecular role of c-Myc in head and neck squamous cell carcinoma (HNSC) remains unclear.MethodsSeveral biological databases, including UALCAN, TIMER2.0, TCGAportal, GEPIA, KM plotter, OncoLnc, LinkedOmics, GSCA, and TCIA, were used to analyze the molecular role of c-Myc in HNSC. The expression levels of c-Myc were validated by real-time PCR (RT–PCR) and Western blot in CAL-27 cells.ResultsThe expression of c-Myc mRNA were significantly increased in HPV-negative HNSC tissues. The expression of c-Myc gene level was correlated with TP53 mutation status. HNSC also showed hypomethylated c-Myc compared with normal tissues. c-Myc was identified as an ominous prognostic factor for HNSC patients and correlated with immune infiltrating levels. Moreover, high c-Myc expression was associated with decreased expression of a series of immune checkpoints, resulting in a dampened immune response. c-Myc potentially mediated IL-17 signaling pathway and Th1 and Th2 cell differentiation. Inhibition of c-Myc expression increased apoptosis of CAL-27 cells.ConclusionsThese findings suggest a new mechanism of c-Myc in the prognosis of HNSC, implying the potential of c-Myc as a therapeutic target for HNSC patients.

A cuproptosis and copper metabolism-related gene prognostic index for head and neck squamous cell carcinoma.

BackgroundThe purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism–related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC).MethodsThe details of human cuproptosis and copper metabolism–related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed.ResultsThe 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC.ConclusionsOur results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.

IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics.

IQGAP1 (IQ motif-containing GTPase-activating protein 1) scaffolds several signaling pathways in mammalian cells that are implicated in carcinogenesis, including the RAS and PI3K pathways that involve multiple protein kinases. IQGAP1 has been shown to promote head and neck squamous cell carcinoma (HNSCC); however, the underlying mechanism(s) remains unclear. Here, we report a mass spectrometry-based analysis identifying differences in phosphorylation of cellular proteins in vivo and in vitro in the presence or absence of IQGAP1. By comparing the esophageal phosphoproteome profiles between Iqgap1+/+ and Iqgap1-/- mice, we identified RNA splicing as one of the most altered cellular processes. Serine/arginine-rich splicing factor 6 (SRSF6) was the protein with the most downregulated levels of phosphorylation in Iqgap1-/- tissue. We confirmed that the absence of IQGAP1 reduced SRSF6 phosphorylation both in vivo and in vitro. We then expanded our analysis to human normal oral keratinocytes. Again, we found factors involved in RNA splicing to be highly altered in the phosphoproteome profile upon genetic disruption of IQGAP1. Both the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Cancer Genome Atlas (TCGA) data sets indicate that phosphorylation of splicing-related proteins is important in HNSCC prognosis. The Biological General Repository for Interaction Datasets (BioGRID) repository also suggested multiple interactions between IQGAP1 and splicing-related proteins. Based on these collective observations, we propose that IQGAP1 regulates the phosphorylation of splicing proteins, which potentially affects their splicing activities and, therefore, contributes to HNSCC. Raw data are available from the MassIVE database with identifier MSV000087770.

The expression and role of tubulin polymerization-promoting protein 3 in oral squamous cell carcinoma

ObjectiveTo study the expression, prognostic landscape, and the function of tubulin polymerization-promoting protein 3 (TPPP3) in oral squamous cell carcinoma (OSCC) and explore the relationship between TPPP3 expression and immune infiltration. DesignImmunohistochemical analysis using tissue microarray of 65 OSCC samples and 10 normal oral mucosa samples was performed to explore the expression levels in OSCC. 5 OSCC samples and 5 adjacent normal oral mucosa samples were selected to further analyze the expression levels by western blot. Some online bioinformatics analysis tools were adopted to study the transcriptome and prognostic landscape of TPPP3, the relationship of TPPP3 expression with immune infiltration, and the most possible “functions and pathways” of TPPP3 in head and neck squamous cell carcinoma (HNSC). ResultsImmunohistochemical, western blot and bioinformatics analysis showed that the expression of TPPP3 in OSCC was significantly lower than that in the normal oral mucosa. High expression of TPPP3 was associated with a good prognosis of HNSC. TPPP3 expression was significantly positively correlatedwith infiltration level of B cell plasma and myeloid dendritic cells activated in HNSC, while it was negatively correlated with infiltration level of Tregs cells, CD8+ T cells, B cell memory. Pathway analysis results revealed one most probable function and two significant pathways in which TPPP3 participates. ConclusionsTPPP3 can serve as a potential diagnostic biomarker and a prognostic protective indicator of OSCC. It plays an important role in the recruitment and regulation of tumor-infiltrating immune cells, which may affect the survival of patients.