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Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

ABSTRACT: Background:Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related death in men. Immune responses in the tumor microenvironment are hypothesized to be related to the prognosis of PCa patients; however, no studies are available to confirm the same. In this study, we aimed to explore the potential link between these two factors and identify new biomarkers to estimate the survival rate of PCa patients. Methods:A total of 490 cases were obtained from The Cancer Genome Atlas (TCGA) database. The gene expression data were analyzed by the ESTIMATE algorithm to evaluate the immune and stromal scores. The survival rate was calculated according to the case-specific clinical data. Enrichment analysis was performed to discover the main biological processes and signaling pathways of immune responses. We further identified and analyzed hub genes in the protein-protein interaction (PPI) network and evaluated their prognostic values. Results:Immune score significantly correlated with immune cell infiltration and overall survival of PCa patients. The genes CXCR4 and GPR183, identified as hub genes in the PPI network, correlated with immune cell infiltration and prognosis of PCa patients. Conclusion:CXCR4 and GPR183 participate in immune cell infiltration and function in PCa patients. The immune score, as well as the expression of CXCR4 and GPR183 in prostate cancer tissues, could be potential indexes for the prognosis of prostate cancer.

SUBMITTER: Sun W

PROVIDER: S-EPMC7662134 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

Sun Wenguo W Shi Hailin H Yuan Zhen Z Xia Li L Xiang Xuebao X Quan Xiangfeng X Shi Wenjie W Jiang Leiming L

Frontiers in oncology 20201030

<h4>Background</h4>Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related death in men. Immune responses in the tumor microenvironment are hypothesized to be related to the prognosis of PCa patients; however, no studies are available to confirm the same. In this study, we aimed to explore the potential link between these two factors and identify new biomarkers to estimate the survival rate of PCa patients.<h4>Methods</h4>A total of 490 cases were ob ...[more]

PMID: 33194726

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Project description:BackgroundBreast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.MethodsThe stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database.ResultsAlthough the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.ConclusionsHigh CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.

Project description:AbstractThe tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.

Dataset Information

Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

Publications

Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

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