Dataset Information

The prognostic value of the proteasome activator subunit gene family in skin cutaneous melanoma.

ABSTRACT: Background: The functional significance of the proteasome activator subunit (PSME) gene family in the pathogenesis of skin cutaneous melanoma (SKCM) remains to be elucidated. Materials and methods: Clinical data for patients with SKCM, including expression levels of PSME genes, were extracted from TCGA. GO term and KEGG pathway enrichment analyses were performed. Correlations between the expression levels of PSME genes in SKCM were evaluated with the Pearson correlation coefficient. Functional and enrichment analyses were conducted using DAVID. Univariate and multivariate survival analyses adjusted by Cox regression were used to construct a prognostic signature. The mechanisms underlying the association between PSME gene expression and overall survival (OS) were explored with gene set enrichment analysis. Joint-effects survival analysis was performed to evaluate the clinical value of the prognostic signature. Results: The median expression levels of PSME1, PSME2 and PSME3 were significantly higher in SKCM than in normal skin. PSME1, PSME2, and PSME3 were significantly enriched in several biological processes and pathways including cell adhesion, adherens junction organization, regulation of autophagy, cellular protein localization, the cell cycle, apoptosis, and the Wnt and NF-?B pathways. High expression levels of PSME1 and PSME2 combined with a low expression level of PSME3 was associated with favorable OS. Conclusion: Knowledge of the expression levels of the PSME gene family could provide a sensitive strategy for predicting prognosis in SKCM.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6584401 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The prognostic value of the proteasome activator subunit gene family in skin cutaneous melanoma.

Wang Qiaoqi Q Pan Fuqiang F Li Sizhu S Huang Rui R Wang Xiangkun X Wang Shijun S Liao Xiwen X Li Dong D Zhang Liming L

Journal of Cancer 20190522 10

Background: The functional significance of the proteasome activator subunit (PSME) gene family in the pathogenesis of skin cutaneous melanoma (SKCM) remains to be elucidated. Materials and methods: Clinical data for patients with SKCM, including expression levels of PSME genes, were extracted from TCGA. GO term and KEGG pathway enrichment analyses were performed. Correlations between the expression levels of PSME genes in SKCM were evaluated with the Pearson co ...[more]

PMID: 31258724

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Project description:BackgroundThe like-Smith (LSM) family is a group of RNA-binding proteins involved in RNA metabolism. However, their involvement in tumors, particularly skin cutaneous melanoma (SKCM), is not fully understood. In this study, we focused on the expression profiles and prognostic values of the LSM family in SKCM.MethodsRaw data were downloaded from The Cancer Genome Atlas. The expression profile and prognostic value of LSM genes in SKCM were explored using the GEPIA, cBioPortal, and HPA databases. Protein-protein and gene-gene interaction analyses were performed using STRING and GeneMANIA. Enrichment and Cox regression analysis were conducted using R software. The TISIDB database was used to explore the relationship between LSMs and immunomodulators. Receiver operating characteristic curves and nomogram models were constructed to validate prognostic values.ResultsmRNA and protein expression levels of LSM2, LSM4, and LSM12 were significantly elevated in SKCM. The upregulated mRNA expression of LSM2 (p = 0.0013) and LSM4 (p = 0.0043) was significantly correlated with poor overall survival in patients with SKCM, whereas only LSM2 (p = 0.049) overexpression was markedly associated with worse disease-free survival. LSM2 overexpression was an independent risk factor (p = 0.013) and was confirmed to have a high prognostic value in SKCM using the receiver operating characteristic curve (AUC = 0.942) and nomogram models. All LSM genes were identified as genomic mutations, whereas alteration of LSM2 (p = 0.0153) significantly affected the overall survival in patients with SKCM. Significant correlations were observed between LSM family expression, immune cell infiltration, and immunomodulator. Furthermore, function and pathway enrichment analysis showed that the LSM family was mainly RNA binding proteins and involved in RNA splicing and degradation.ConclusionExpression profiles and prognostic values of LSM in SKCM were inconsistent. Among the LSM family, only LSM2 may serve as a potential poor prognosticator and immunotherapeutic target of SKCM.

Project description:Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear. Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM. Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC. Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.

Dataset Information

The prognostic value of the proteasome activator subunit gene family in skin cutaneous melanoma.

Publications

The prognostic value of the proteasome activator subunit gene family in skin cutaneous melanoma.

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