Integrated analysis of the prognostic values of RNA ‐binding proteins in head and neck squamous cell carcinoma

BioFactors ◽  
2021 ◽  
Author(s):  
Zeng‐Hong Wu ◽  
Jian‐Xin Yue ◽  
Tao Zhou ◽  
Hong‐Jun Xiao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Guangsheng Hu ◽  
Qingshan Jiang ◽  
Lijun Liu ◽  
Hong Peng ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Risk Model ◽  
Rna Binding Proteins ◽  
Integrated Analysis

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.

scholarly journals Integrated Analysis Reveals ENDOU as a Biomarker in Head and Neck Squamous Cell Carcinoma Progression

2021 ◽  
Vol 10 ◽  
Author(s):  
Chengzhi Xu ◽  
Yunbin Zhang ◽  
Yupeng Shen ◽  
Yong Shi ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis ◽  
And Migration ◽  
Proliferation And Migration

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a leading cancer with high morbidity and mortality worldwide. The aim is to identify genes with clinical significance by integrated bioinformatics analysis and investigate their function in HNSCC.MethodsWe downloaded and analyzed two gene expression datasets of GSE6631 and GSE107591 to screen differentially expressed genes (DEGs) in HNSCC. Common DEGs were functionally analyzed by Gene ontology and KEGG pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed with STRING database and Cytoscape. ENDOU was overexpressed in FaDu and Cal-27 cell lines, and cell proliferation and migration capability were evaluated with MTT, scratch and transwell assay. The prognostic performance of ENDOU and expression correlation with tumor infiltrates in HNSCC were validated with TCGA HNSCC datasets.ResultsNinety-eight genes shared common differential expression in both datasets, with core functions like extracellular matrix organization significantly enriched. 15 genes showed prognostic significance, and COBL and ENDOU serve as independent survival markers in HNSCC. In-vitro ENDOU overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated ENDOU down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. ENDOU showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, ENDOU showed negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.ConclusionThis study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

Autophagy regulation patterns characterization identifies immune phenotypes and immunotherapy response in head and neck squamous cell carcinoma (HNSCC)

2020 ◽  
Author(s):  
Bo Ma ◽  
Hui Li ◽  
Mingzhu Zheng ◽  
Rui Cao ◽  
Riyue Yu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Scoring System ◽  
Clustering Algorithm ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis ◽  
Molecular Characteristics ◽  
Immune Phenotypes

Abstract BackgroundAutophagy degraded and recycled cytoplasmic components to maintain cellular homeostasis under stress conditions, which was recognized as double-edged sword in oncogenesis and novel target in cancer treatment. However, comprehensive analysis of the relationship between autophagy regulation and immunity has not been reported yet. MethodsUnsupervised consensus clustering algorithm was used to identify autophagy regulation patterns. LASSO cox regression algorithm was used to build a scoring system (ATGscore) to represent the individual autophagy regulation pattern. Then integrated analysis of autophagy regulation patterns and ATGscore was performed.ResultsWe have successful depicted five autophagy regulation patterns and established a scoring system (ATGscore) to represent it, which was shown to be significantly correlated with TIME infiltration, immune phenotypes, molecular subtypes, and genetic variation, etc. in 1165 head and neck squamous cell carcinoma (HNSCC) patients. Moreover, ATGscore was an independent prognostic factor and potent predictor for clinical response to immune-checkpoint inhibitors (ICIs) targeting immunotherapy. ConclusionUnderstanding the molecular characteristics of autophagy regulation patterns in HNSCC could help us to depict the underlying mechanism of tumour immunity and lay a solid foundation on combination of autophagy targeting therapies and immunotherapies for clinical application in HNSCC.

scholarly journals Integrated analysis of deregulation microRNA expression in head and neck squamous cell carcinoma

Medicine ◽  
2021 ◽  
Vol 100 (6) ◽  
pp. e24618
Author(s):  
Cheng-Lin Qi ◽  
Jian-Fei Sheng ◽  
Mao-Ling Huang ◽  
You Zou ◽  
Yong-Ping Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Microrna Expression ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis

scholarly journals A Novel Prognostic Model for Oral Squamous Cell Carcinoma: The Functions and Prognostic Values of RNA-Binding Proteins

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingjuan Lu ◽  
Yongcong Yan ◽  
Bowen Li ◽  
Mo Liu ◽  
Yancan Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Prognostic Model ◽  
Binding Proteins ◽  
Rna Binding ◽  
Cox Regression ◽  
Rna Binding Proteins

PurposeThe biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC using several bioinformatic strategies.Materials and MethodsOSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs using Cox regression and risk score analyses.ResultsWe found that the differentially expressed RBPs were closely related to the defense response to viruses and multiple RNA processes. We identified 10 prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the receiver operating characteristic (ROC) curve (AUC) of the risk score model was 0.781, suggesting that our model exhibited excellent prognostic performance. Finally, we built a nomogram integrating the 10 RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC.ConclusionWe established a novel 10-RBP-based model for OSCC that could enable precise individual treatment and follow-up management strategies in the future.

scholarly journals HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jian Wang ◽  
Hao Sun ◽  
Qin Zeng ◽  
Xue-Jun Guo ◽  
Hui Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis ◽  
Immune Microenvironment ◽  
Hpv Status

Abstract Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.

scholarly journals MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ankit P. Jain ◽  
Krishna Patel ◽  
Sneha Pinto ◽  
Aneesha Radhakrishnan ◽  
Vishalakshi Nanjappa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Acquired Resistance ◽  
Unmet Need ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis

AbstractEpidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, quantitative proteomic and phosphoproteomic profiling. We observed amplification of several genes including AXL kinase and transcription factor YAP1 resulting in protein overexpression. We also observed expression of constitutively active mutant MAP2K1 (p.K57E) in erlotinib resistant SCC-R cells. An integrated analysis of genomic, proteomic and phosphoproteomic data revealed alterations in MAPK pathway and its downstream targets in SCC-R cells. We demonstrate that erlotinib-resistant cells are sensitive to MAPK pathway inhibition. This study revealed multiple genetic, proteomic and phosphoproteomic alterations associated with erlotinib resistant SCC-R cells. Our data indicates that therapeutic targeting of MAPK pathway is an effective strategy for treating erlotinib-resistant HNSCC tumors.

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