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A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

ABSTRACT: Prostate cancer (PCa) is one of the most deadly urinary tumors in men globally, and the 5-year over survival is poor due to metastasis of tumor. It is significant to explore potential biomarkers for early diagnosis and personalized therapy of PCa. In the present study, we performed an integrated analysis based on multiple microarrays in the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed genes (DEGs) between 510 PCa and 259 benign issues. The weighted correlation network analysis indicated that prognostic profile was the most relevant to DEGs. Then, univariate and multivariate COX regression analyses were conducted and four prognostic genes were obtained to establish a four-gene prognostic model. And the predictive effect and expression profiles of the four genes were well validated in another GEO dataset, The Cancer Genome Atlas and the Human Protein Atlas datasets. Furthermore, combination of four-gene model and clinical features was analyzed systematically to guide the prognosis of patients with PCa to a largest extent. In summary, our findings indicate that four genes had important prognostic significance in PCa and combination of four-gene model and clinical features could achieve a better prediction to guide the prognosis of patients with PCa.

SUBMITTER: Yuan P

PROVIDER: S-EPMC7643642 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

Yuan Penghui P Ling Le L Fan Qing Q Gao Xintao X Sun Taotao T Miao Jianping J Yuan Xianglin X Liu Jihong J Liu Bo B

Cancer medicine 20200913 21

Prostate cancer (PCa) is one of the most deadly urinary tumors in men globally, and the 5-year over survival is poor due to metastasis of tumor. It is significant to explore potential biomarkers for early diagnosis and personalized therapy of PCa. In the present study, we performed an integrated analysis based on multiple microarrays in the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed genes (DEGs) between 510 PCa and 259 benign issues. The weighted correlation netw ...[more]

PMID: 32924329

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Project description:BackgroundUveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM.MethodsUM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan-Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan-Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment.ResultsA seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature.ConclusionsIn this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.

Project description:BackgroundPyroptosis is a form of cell death characterized by cell swelling and plasma membrane bubbling in association with inflammatory and immune responses. To date, the association between pyroptosis and colorectal cancer remains unclear. We aimed to establish a novel pyroptosis-associated model for the prognosis of colorectal cancer.MethodsPyroptosis-related genes were extracted using Gene Set Enrichment Analysis. A least absolute shrinkage and selection operator regression model was constructed to identify a pyroptosis-related gene signature using the Cancer Genome Atlas and Gene Expression Omnibus databases. Then, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology and GSEA were performed to better understand the potential mechanisms and the functional pathways associated with pyroptosis involved in colorectal cancer. The relationship between the pyroptosis-related signature and immune infiltration was investigated using Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts and MCPcounter.ResultsA 12 pyroptosis-related gene signature was identified. Then, patients were classified into high- and low-risk groups. Kaplan-Meier and receiver operating characteristic analyses confirmed that the high-risk groups showed worse overall survival, progression-free survival, or relapse-free survival probability. Functional enrichment analysis showed that pyroptosis was associated with extracellular matrix-related pathways. Furthermore, the pyroptosis risk score was associated with immune infiltration. The low-risk group exhibited a higher percentage of plasma cells, CD4 T cells, activated dendritic cells, and activated mast cells. M2 macrophages and M0 macrophages were positively related to the risk score.ConclusionOur research yielded a novel pyroptosis-related prognostic signature for colorectal cancer that was related to immune cell infiltration, and it provided an immunological perspective for developing personalized therapies.

Project description:The cyclic GMP-AMP synthase-stimulator of the interferon genes (cGAS-STING) pathway is essential in inflammation-driven tumor occurrence and progression. However, the prognostic roles and immune functions of cGAS-STING pathway-related genes in patients with prostate adenocarcinoma (PRAD) remain unclear. cGAS-STING pathway-related genes were obtained from the gene set enrichment analysis (GSEA) website. Univariate Cox regression analysis was performed to screen the prognosis-related hub genes in the cancer genome atlas (TCGA) and GSE116918 datasets. Unsupervised clustering analysis was performed to identify different clusters. The least absolute shrinkage and selection operator and multivariate Cox regression analyses were applied to develop a prognostic risk model. The prognostic values and predictive performance of risk signature were assessed by the Kaplan-Meier curve and receiver operating characteristic curve. The IMvigor210 cohort was used to investigate the potential values of the risk score in immunotherapeutic responses. Two clusters were identified based on the expression matrix of 12 prognosis-related genes. Specifically, better overall survival was observed in cluster 2 than cluster 1 in both datasets. Inflammation-related pathway enrichment and immune cell infiltration levels were altered between 2 clusters. Moreover, 6 genes (CASP8, GRK6, IL3RA, PLCB1, TBKBP1, and TNFSF10) were identified to generate a cGAS-STING pathway-related signature (CPRS). Survival analysis showed that patients in the high-risk group showed a more dismal survival than those in the low-risk group in TCGA and GSE116918 datasets. Notably, the CPRS can differentiate responsive patients from non-responsive individuals treated with PD-L1 blockades in an independent cohort. In addition, higher CPRS was associated with a more favorable prognosis. The proposed risk model was developed based on 6 cGAS-STING pathway related-genes, which can be used as a promising predictor for patient survival and immunotherapeutic responses in PRAD, contributing to treatment strategy-related decision-making.

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A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

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A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

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