Dataset Information

The Immune Landscape and Prognostic Immune Key Genes Potentially Involved in Modulating Synaptic Functions in Prostate Cancer.

ABSTRACT: Background: Increasing evidence has indicated an association between differentially expressed genes (DEGs) in tumor-infiltrating immune cells (TIICs) and clinical outcome. The aim of this research is to investigate the influence of tumor microenvironment on the gene expression profile of TIICs and to identify their potential markers for modulating immune cell function in prostate cancer. Methods: In our research, CIBERSORT algorithm was utilized to calculate the proportion of the TIICs in 164 tumor and 18 control samples from The Cancer Genome Atlas cohort. The differential expression analysis was conducted using R, and then the functional and the pathway enrichments of the DEGs were analyzed using Database for Annotation, Visualization, and Integrated Discovery, followed by integrated regulatory network analysis. Results: As a result, nTreg, B cells, Th1, and DC cells were significantly increased, accompanied by largely decreased NK and NKT cells. The expressed immune-related gene correlation analysis showed that the signature gene expression extent of CD8 T cells was positively associated with CD4 memory activated T cells but negatively correlated with that of CD4 memory resting T cells. In addition, a total of 128 differentially expressed genes were identified. CytoHubba analysis obtained six hub genes, of which three prognostic-associated potential key molecules including CAV1, FLNA, and VCL were mainly involved in biological processes associated with the regulation of organic substance and synaptic connections. Conclusions: This study provides a comprehensive understanding of the landscape of TIICs and the roles of the hub genes which may be valuable markers in prostate cancer diagnosis and immunotherapy.

SUBMITTER: Zhu S

PROVIDER: S-EPMC7456865 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Immune Landscape and Prognostic Immune Key Genes Potentially Involved in Modulating Synaptic Functions in Prostate Cancer.

Zhu Sha S Han Xu X Qiao Xianli X Chen Shengxian S

Frontiers in oncology 20200814

<b>Background:</b> Increasing evidence has indicated an association between differentially expressed genes (DEGs) in tumor-infiltrating immune cells (TIICs) and clinical outcome. The aim of this research is to investigate the influence of tumor microenvironment on the gene expression profile of TIICs and to identify their potential markers for modulating immune cell function in prostate cancer. <b>Methods:</b> In our research, CIBERSORT algorithm was utilized to calculate the proportion of the T ...[more]

PMID: 32923385

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Project description:BackgroundRecently, an increasing number of studies have uncovered the aberrant expression of methyltransferase-like family (METTL) plays an important role in tumorigenesis, such as METTL3 (an m6A writer). In our recent work, we discovered METTL24 expression was highly associated with the hazard ratio (HR) of kidney renal clear cell carcinoma (KIRC) compared to other tumors, implying a special function of METTL24 in KIRC carcinogenesis. Until now, the functions and mechanisms of METTL24 in KIRC have remained mostly unknown.MethodsThe mRNA expression of METTL24 in KIRC was analyzed using the TIMER 2.0, GEPIA, and UALCAN databases. The immunohistochemical assay was performed to validate METTL24 expression in our self-built Chinese cohort (n tumor = 88, n normal = 85). The gene set enrichment analysis (GSEA) was used to investigate the biological processes in which METTL24 might be engaged. The Spearman analysis was used to evaluate the expression correlations between METTL24 and a range of immunological variables, and the effects of METTL24 on the infiltration levels of multiple immune cells were explored using TCGA data. The upstream transcription factors of METTL24 were screened through a multi-omics analysis.ResultsMETTL24 expression in KIRC tissues was significantly decreased compared to normal adjacent kidney tissues, which was associated with the lower survival rate of KIRC patients. METTL24 potentially participated in the immune-relevant biological processes such as cytokine binding, NF-kappa B binding, MHC protein complex, and interleukin-12 action. Besides, METTL24 expression was linked to a number of immune checkpoints, cytokines, chemokines, and chemokine receptors, and also correlated with the infiltration levels of 10 types of immune cells in KIRC. Meanwhile, METTL24 expression differently affected the overall survival rates (OS) of KIRC patients with high or low levels of immune infiltration. Finally, CTCF and EP300 were discovered to be the probable transcription factors of METTL24 in KIRC.ConclusionThis study revealed that METTL24 might serve as a prognostic marker in KIRC and as one immune-relevant target for clinical treatment.

Project description:BackgroundThis study was to explore the infiltration pattern of immune cells in the prostate cancer (PCa) microenvironment and evaluate the possibility of specific infiltrating immune cells as potential prognostic biomarkers in PCa.MethodsInfiltrating percentage of 22 immune cells were extracted from 27 normalized datasets by CIBERSORT algorithm. Samples with CIBERSORT p-value < 0.05 were subsequently merged and divided into normal or tumor groups. The differences of 22 immune cells between normal and tumor tissues were analyzed along with potential infiltrating correlations among 22 immune cells and Gleason grades. SNV data from TCGA was used to calculate the TMB score. A univariate and multivariate regression were used to evaluate the prognostic effects of immune cells in PCa.ResultsTen immune cells with significant differences were identified, including seven increased and three decreased infiltrating immune cells from 190 normal prostate tissues and 537 PCa tissues. Among them, the percentage of infiltration of resting NK cells increased the most, whereas the percentage of infiltration of resting mast cells decreased the most. In normal tissues, CD8+ T cells had the strongest infiltrating correlation with monocytes, while activated NK cells and naive B cells were the highest in PCa tissues. Moreover, the infiltration of five immune cells was significantly associated with TMB score and mutations of immune gene change the infiltration of immune cells. The Area Under Curve (AUC) of the multivariate regression model for the five- and 10-year survival prediction of PCa reached 0.796 and 0.862. The validation cohort proved that the model was reproducible.ConclusionsThis study demonstrated that different infiltrating immune cells in prostate cancer, especially higher infiltrating M1 macrophages and neutrophils in PCa tissue, are associated with patients' prognosis, suggesting that these two immune cells might be potential targets for PCa diagnosis and prognosis of treatment.

Dataset Information

The Immune Landscape and Prognostic Immune Key Genes Potentially Involved in Modulating Synaptic Functions in Prostate Cancer.

Publications

The Immune Landscape and Prognostic Immune Key Genes Potentially Involved in Modulating Synaptic Functions in Prostate Cancer.

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