Dataset Information

Comprehensive Analysis of Tumor Immune Microenvironment Characteristics for the Prognostic Prediction and Immunotherapy of Oral Squamous Cell Carcinoma.

ABSTRACT: Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of oral and maxillofacial region. A recent clinical research has shown that tumor immune microenvironment (TIME)cells are closely related to immunotherapy sensitivity and OSCC prognosis. Nonetheless, a comprehensive analysis of TIME in OSCC has not been reported. Methods: Bioinformatics and computational algorithms were employed to determine the significance of TIME cells in 257 OSCC patients. TIME scores were measured by three TIME models, and then used to evaluate the prognosis of OSCC patients. Results: High TIME score was characterized by better prognosis in OSCC patients less than 60 years old, overexpression of immunotherapy targets (e.g., PD-1 and CLTA-4), and higher T-cell activity to inhibit tumor growth. Besides, poor prognosis was associated with low time score. Conclusion: TIME score exhibited potential as a prognostic biomarker and an indicator in predict immunotherapeutic outcomes. Through the understanding of TIME model, this study can provide a better scheme for immunotherapy as the effective treatment of OSCC patients in the future.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC9024147 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Comprehensive Analysis of Tumor Immune Microenvironment Characteristics for the Prognostic Prediction and Immunotherapy of Oral Squamous Cell Carcinoma.

Zhao Yijie Y Chen Dongyi D Yin Junhao J Xie Jian J Sun Chun-Yu CY Lu Mengmeng M

Frontiers in genetics 20220408

<b>Background:</b> Oral squamous cell carcinoma (OSCC) is the most common cancer of oral and maxillofacial region. A recent clinical research has shown that tumor immune microenvironment (TIME)cells are closely related to immunotherapy sensitivity and OSCC prognosis. Nonetheless, a comprehensive analysis of TIME in OSCC has not been reported. <b>Methods:</b> Bioinformatics and computational algorithms were employed to determine the significance of TIME cells in 257 OSCC patients. TIME scores wer ...[more]

PMID: 35464860

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Project description:Lung squamous cell carcinoma (LUSC) is a common subtype of lung cancer that exhibits diverse pyroptosis regulatory patterns. Studies have highlighted the significance of pyroptosis in cancer invasion and immune responses. We aimed to explore the signatures of pyroptosis-related genes and their immune relevance in LUSC. Using The Cancer Genome Atlas (TCGA)-LUSC cohort and 5 gene expression omnibus (GEO) datasets, we performed consensus clustering based on 41 pyroptosis-related genes, and single sample gene set enrichment analysis (ssGSEA) was employed to calculate the infiltration levels of distinct clusters. A pyroptosis scoring scheme using the principal component analysis (PCA) method was used to quantify pyroptosis regulation in patients with LUSC and predict their prognosis. Four pyroptosis clusters were identified among 833 LUSC samples, which were associated with different Kyoto encyclopedia of genes and genome (KEGG) signaling pathways and tumor microenvironment infiltration features, and were highly consistent with 4 reported immune phenotypes: immune-responsive, immune-non-functional, immune-exclusion, and immune-ignorance. We then divided the patients into high- and low-pyroptosis score subgroups, and patients with higher scores were characterized by prolonged survival and attenuated immune infiltration. Moreover, higher scores were correlated with male patients, higher microsatellite instability, lower immune checkpoint inhibitor expression (such as CTLA-4 and GAL-9), and high mutation rates of typical mutated genes (e.g., TP53 and TTN). In particular, patients with lower pyroptosis scores showed better immune response to immune checkpoint inhibitor treatment. Pyroptosis regulatory patterns in the immune microenvironment can predict the clinical outcomes of patients with LUSC. Accurately quantifying the pyroptosis of individual patients will strengthen the understanding of heterogeneity within the LUSC tumor microenvironment infiltration areas.

Project description:BackgroundOral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated.Materials and methodsGene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs).ResultsIn this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration.ConclusionIn summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

Dataset Information

Comprehensive Analysis of Tumor Immune Microenvironment Characteristics for the Prognostic Prediction and Immunotherapy of Oral Squamous Cell Carcinoma.

Publications

Comprehensive Analysis of Tumor Immune Microenvironment Characteristics for the Prognostic Prediction and Immunotherapy of Oral Squamous Cell Carcinoma.

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