scholarly journals Prognostic Significance of STC2 and DNA methylation in Head and Neck Squamous Cell Carcinoma: A Study Based on the TCGA and GEO Databases

2021 ◽  
Author(s):  
Guangyao Li ◽  
Daquan Wu ◽  
Lei Zhou ◽  
Dan You ◽  
Xinsheng Huang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Survival Rate ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tp53 Mutation ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Background: Head and neck squamous cell carcinoma (HNSC) is a popular malignancy type that brings about poor prognosis with a low survival rate worldwide. Stanniocalcin 2 (STC2) is a glycosylated peptide hormone and shows the potential to become a new biomarker for the evaluation of malignant tumors. The purpose of this study was to explore the prognostic implications of STC2 and DNA methylation in HNSC and the role of STC2 expression in immune cell infiltration.Methods: STC2 gene expression data were collected from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Univariate and multivariate analyses were employed to screen prognostic risk factors. The relationship between STC2 expression and TP53 mutation in HNSC was explored. TCGA data were utilized to analyze how STC2 expression affected immune cell infiltration in HNSC.Results: STC2 was highly expressed in HNSC patients (P < 0.01), especially those with a lower overall survival rate (P < 0.0001). TP53 mutation might be a risk factor of STC2 overexpression in HNSC (P = 0.0015). STC2 expression was negatively correlated with STC2 methylation (Spearman: -0.43, P < 0.001). Hypermethylation or hypomethylation at the eight CpG sites most related to STC2 expression was identified as independent factors for HNSC prognosis. STC2 was positively correlated with cancer-associated fibroblasts infiltration and associated with the infiltration of various immune cells.Conclusion: STC2 can be regarded as a vital prognostic biomarker of HNSC due to its essential roles in immune cell infiltration.

scholarly journals Characterization of the immune cell infiltration landscape in head and neck squamous cell carcinoma to aid immunotherapy

2020 ◽  
Author(s):  
Xinhai Zhang ◽  
Tielou Chen ◽  
Boxin Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Stromal Component

Abstract Background: The tumor microenvironment chiefly consists of tumor cells, and tumor-infiltrating immune cells admixed with the stromal component. The recent clinical trial has shown that the tumor immune cell infiltration is correlated with the sensitivity to immunotherapy and the prognosis of head and neck squamous cell carcinoma (HNSC). However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Methods: We proposed two computational algorithms to unravel the immune infiltration landscape of 1029 HNSC patients. The Boruta algorithm and principal component algorithms (PCA) were employed to quantify three immune cell infiltration gene subtypes categorized as per the immune cell infiltrations pattern. Results: The high ICI score subtype was characterized by a higher tumor mutation burden (TMB) and the immune-activated signaling pathway. However, a low ICI score subtype was categorized as per the activation of immunosuppressive signaling pathways such as TGF-BETA, WNT signaling pathway, and lower TMB. Two immunotherapy cohorts confirmed patients with higher ICI score demonstrated significant therapeutic advantages and clinical benefits.Conclusions: This demonstrated that the ICI score could serve as an effective prognostic biomarker and predictive indicator for immunotherapy. A comprehensive understanding of the HNSC immune landscape might help in tailoring immunotherapeutic strategies for different patients.

Integrated Bioinformatics Analysis of Differentially-Expressed Genes and Immune Cell Infiltration Characteristics in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Zitong Feng ◽  
Jingge Qu ◽  
Xiao Liu ◽  
Jinghui Liang ◽  
Yongmeng Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a significant challenge. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identified by the “limma” R package, and a total of 152 robust DEGs were identified by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were significantly associated with extracellular matrix related process. Immune cell infiltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC.

scholarly journals Identification of Immune-related lncRNA Panel for Predicting Immune Checkpoint Blockade and Prognosis in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chongchang Zhou ◽  
Guowen Zhan ◽  
Zhisen Shen ◽  
Yi Shen ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Risk Model ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs impact every step of cancer immunity. Therefore, reliable immune-lncRNA able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Altas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, chemotherapeutic and immunotherapeutic efficacy between two groups. Our results constructed a risk model consisted of 18 DEir-lncRNA pairs showing significantly association with survival of patients with HNSCC. Besides, HNSCC patients with low risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. In summary, our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

scholarly journals Characterization of Molecular Subtypes in Head and Neck Squamous Cell Carcinoma With Distinct Prognosis and Treatment Responsiveness

2021 ◽  
Vol 9 ◽  
Author(s):  
Pei Zhang ◽  
Shue Li ◽  
Tingting Zhang ◽  
Fengzhen Cui ◽  
Ji-Hua Shi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Oncogenic Signaling ◽  
Mtorc1 Signaling

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies with complex phenotypic, etiological, biological, and clinical heterogeneities. Previous studies have proposed different clinically relevant subtypes of HNSCC, but little is known about its corresponding prognosis or suitable treatment strategy. Here, we identified 101 core genes from three prognostic pathways, including mTORC1 signaling, unfold protein response, and UV response UP, in 124 pairs of tumor and matched normal tissues of HNSCC. Moreover, we identified three robust subtypes associated with distinct molecular characteristics and clinical outcomes using consensus clustering based on the gene expression profiles of 944 HNSCC patients from four independent datasets. We then integrated the genomic information of The Cancer Genome Atlas (TCGA) HNSCC cohort to comprehensively evaluate the molecular features of different subtypes and screen for potentially effective therapeutic agents. Cluster 1 had more arrested oncogenic signaling, the highest immune cell infiltration, the highest immunotherapy and chemotherapeutic responsiveness, and the best prognosis. By contrast, Cluster 3 showed more activated oncogenic signaling, the lowest immune cell infiltration, the lowest immunotherapy and chemotherapy responsiveness, and the worst prognosis. Our findings corroborate the molecular diversity of HNSCC tumors and provide a novel classification strategy that may guide for prognosis and treatment allocation.

scholarly journals Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

2018 ◽  
Vol 57 (9) ◽  
pp. 1165-1172 ◽  
Author(s):  
Karolin Schneider ◽  
Etienne Marbaix ◽  
Caroline Bouzin ◽  
Marc Hamoir ◽  
Pierre Mahy ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Squamous Cell Carcinoma ◽  
Retrospective Study ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Identification of factors related to immunotherapy efficacy and prognosis in patients with advanced head and neck squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xuanli Xu ◽  
Rongrong Li ◽  
Lin Zhang ◽  
Guopei Zhu ◽  
Dandan Ren ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Gene Mutations ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mutation Burden

Abstract Background Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes. Methods Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy. Results Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients. Conclusion HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.

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