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

Zhu, Sha; Han, Xu; Qiao, Xianli; Chen, Shengxian

doi:10.3389/fonc.2020.01330

Cited by 9 publications

(6 citation statements)

References 52 publications

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“…GO analysis was used to evaluate the potential functions and degree of enrichment of the DEGs in biological processes (BP), cellular components (CC), and molecular functions (MF). Kyoto Gene and Genome Encyclopedia (KEGG) database with a P-value of <0.05 was used to systematically analyze the differences in gene function [ 11 ]. In addition, gene set enrichment analysis (GSEA) was used to determine the statistically significant and concordant differences between the two biological states of primary and bone metastatic CRPC tumors.…”

Section: Methodsmentioning

confidence: 99%

Prognostic signatures associated with high infiltration of Tregs in bone metastatic prostate cancer

Meng

Han

Min

et al. 2021

Aging

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Metastatic cancer especially bone metastasis (BM) is the lethal end-stage of castration-resistant prostate cancer (CRPC). To understand the possible molecular mechanisms underlying the development of the distant metastasis is of potential clinical value. We sought to identify differentially expressed genes between patient-matched primary and bone metastatic CRPC tumors. Functional enrichment, protein-protein interaction networks, and survival analysis of DEGs were performed. DEGs with a prognostic value considered as candidate genes were evaluated, followed by genetic analysis of tumor infiltrating immune cells based on Wilcoxon test and immunofluorescence identification. Expression profiles analysis showed that 381 overlapping genes were screened as differentially expressed genes (DEGs), of which 16 DEGs were randomly selected to be validated and revealed that most of these genes showed a transcriptional profile similar to that seen in the datasets (Pearson’s r = 0.76). Six core genes were found to be involved in regulation of extracellular matrix receptor interaction and chemotactic activity, and four of them were significantly correlated with the survival of PCa patients with bone metastases. Immune infiltration analysis showed that the expressions levels of COL3A1, RAC1, FN1, and SDC2 in CD4+T cells were significantly higher than those in tumor cells, especially regulatory T cell infiltration was significantly increased in BM tumors. We analyzed gene expression signatures specifically associated with the development of bone metastases of CRPC patients. Characterization of genes associated with BM of mCRPC is critical for identification of predictive biomarkers and potential therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Prognostic signatures associated with high infiltration of Tregs in bone metastatic prostate cancer

Meng

Han

Min

et al. 2021

Aging

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“…Increasing evidence suggests that polarized NK cells are present in the peripheral blood of patients with several types of cancer (9,10,15,16,29,30,33) and their altered profile could be a relevant feature. The idea that NK cells can be envisaged as biomarkers for PCa have been previously explored (26,(34)(35)(36). Also, a clinical trial is exploring the significance of circulating NK cells in metastatic PCa (https://clinicaltrials.gov/ct2/show/ NCT02963155).…”

Section: Introductionmentioning

confidence: 99%

Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors

et al. 2021

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Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic phenotype/functions. However, there is still a lack of knowledge concerning the phenotype of peripheral blood (PB) NK (pNK) cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized pNK from PCa patients (PCa TA-NKs) and investigated their interactions with endothelial cells and monocytes/macrophages. NK cell subset distribution in PB of PCa patients was investigated, by multicolor flow cytometry, for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Conditioned media (CM) from FACS-sorted PCa pTA-NKs were used to determine their ability to induce pro-inflammatory/pro-angiogenic phenotype/functions in endothelial cells, monocytes, and macrophages. CM from three different PCa (PC-3, DU-145, LNCaP) cell lines, were used to assess their effects on human NK cell polarization in vitro, by multicolor flow cytometry. We found that PCa pTA-NKs acquire the CD56brightCD9+CD49a+CXCR4+ phenotype, increased the expression of markers of exhaustion (PD-1, TIM-3) and are impaired in their degranulation capabilities. Similar effects were observed on healthy donor-derived pNK cells, exposed to conditioned media of three different PCa cell lines, together with increased production of pro-inflammatory chemokines/chemokine receptors CXCR4, CXCL8, CXCL12, reduced production of TNFα, IFNγ and Granzyme-B. PCa TA-NKs released factors able to support inflammatory angiogenesis in an in vitro model and increased the expression of CXCL8, ICAM-1, and VCAM-1 mRNA in endothelial cells. Secretome analysis revealed the ability of PCa TA-NKs to release pro-inflammatory cytokines/chemokines involved in monocyte recruitment and M2-like polarization. Finally, CMs from PCa pTA-NKs recruit THP-1 and peripheral blood CD14+ monocyte and polarize THP-1 and peripheral blood CD14+ monocyte-derived macrophage towards M2-like/TAM macrophages. Our results show that PCa pTA-NKs acquire properties related to the pro-inflammatory angiogenesis in endothelial cells, recruit monocytes and polarize macrophage to an M2-like type phenotype. Our data provides a rationale for a potential use of pNK profiling in PCa patients.

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“…For instance, Cheng C et al claimed RAC3 promoted proliferation, migration, and invasion through PYCR1/JAK/STAT signaling in bladder cancer [ 39 ]. VCL has been reported as an important prognostic biomarker in prostate cancer [ 40 ]. Satow R et al reported that PDGFD promotes aggressiveness in prostate and colorectal cancer [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

Wang

et al. 2022

BMC Cancer

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Background Bladder cancer (BLCA) is the ninth most common cancer globally, as well as the fourth most common cancer in men, with an incidence of 7%. However, few effective prognostic biomarkers or models of BLCA are available at present. Methods The prognostic genes of BLCA were screened from one cohort of The Cancer Genome Atlas (TCGA) database through univariate Cox regression analysis and functionally annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The intersecting genes of the BLCA gene set and focal adhesion-related gene were obtained and subjected to the least absolute shrinkage and selection operator regression (LASSO) to construct a prognostic model. Gene set enrichment analysis (GSEA) of high- and low-risk patients was performed to explore further the biological process related to focal adhesion genes. Univariate and multivariate Cox analysis, receiver operating characteristic (ROC) curve analysis, and Kaplan–Meier survival analysis (KM) were used to evaluate the prognostic model. DNA methylation analysis was presented to explore the relationship between prognosis and gene methylation. Furthermore, immune cell infiltration was assessed by CIBERSORT, ESTIMATE, and TIMER. The model was verified in an external GSE32894 cohort of the Gene Expression Omnibus (GEO) database, and the Prognoscan database presented further validation of genes. The HPA database validated the related protein level, and functional experiments verified significant risk factors in the model. Results VCL, COL6A1, RAC3, PDGFD, JUN, LAMA2, and ITGB6 were used to construct a prognostic model in the TCGA-BLCA cohort and validated in the GSE32894 cohort. The 7-gene model successfully stratified the patients into both cohorts’ high- and low-risk groups. The higher risk score was associated with a worse prognosis. Conclusions The 7-gene prognostic model can classify BLCA patients into high- and low-risk groups based on the risk score and predict the overall survival, which may aid clinical decision-making.

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

Cited by 9 publications

References 52 publications

Prognostic signatures associated with high infiltration of Tregs in bone metastatic prostate cancer

Prognostic signatures associated with high infiltration of Tregs in bone metastatic prostate cancer

Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors

A novel focal adhesion-related risk model predicts prognosis of bladder cancer —— a bioinformatic study based on TCGA and GEO database

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