Dataset Information

Comprehensive investigation of the clinical significance and molecular mechanisms of plasmacytoma variant translocation 1 in sarcoma using genome-wide RNA sequencing data.

ABSTRACT: Objective: The present study aims to identify the potential clinical application and molecular mechanism of plasmacytoma variant translocation 1 (PVT1) in patients with sarcomas by mining an RNA sequencing dataset from The Cancer Genome Atlas (TCGA) through multiple genome-wide analysis approaches. Methods: A genome-wide RNA sequencing dataset was downloaded from TCGA, survival analysis was used to evaluate the prognostic value of PVT1 in sarcoma. The potential mechanism was investigated by multiple tools: Database for Annotation, Visualization, and Integrated Discovery v6.8, gene set enrichment analysis (GSEA), and Connectivity Map (CMap). Results: Comprehensive survival analysis indicated that overexpression of PVT1 was significantly associated with poor prognosis in patients with sarcoma, and nomogram demonstrated that PVT1 contributed more than other traditional clinical parameters in sarcoma survival prediction. Weighted gene co-expression network analysis identified ten hub differentially expressed genes (DEGs) between sarcoma tissues with low and overexpression of PVT1, and substantiated that these DEGs have a complex co-expression network relationship. CMap analysis has identified that antipyrine, ondansetron, and econazole may be candidate targeted drugs for sarcoma patients with PVT1 overexpression. GSEA revealed that overexpression of PVT1 may be involved in the posttranscriptional regulation of gene expression, tumor invasiveness and metastasis, osteoblast differentiation and development, apoptosis, nuclear factor kappa B, Wnt, and apoptotic related signaling pathways. Conclusions: Our findings indicate that PVT1 may serve as a prognostic indicator in patients with sarcoma. Its underlying mechanism is revealed by GSEA, and CMap offers three candidate drugs for the individualized targeted therapy of sarcoma patients with overexpression of PVT1.

SUBMITTER: Liu J

PROVIDER: S-EPMC6775530 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comprehensive investigation of the clinical significance and molecular mechanisms of plasmacytoma variant translocation 1 in sarcoma using genome-wide RNA sequencing data.

Liu Jianwei J Liu Jianwei J Li Rong R Liao Xiwen X Hu Bangli B Yu Jia J

Journal of Cancer 20190827 20

Objective: The present study aims to identify the potential clinical application and molecular mechanism of plasmacytoma variant translocation 1 (PVT1) in patients with sarcomas by mining an RNA sequencing dataset from The Cancer Genome Atlas (TCGA) through multiple genome-wide analysis approaches. Methods: A genome-wide RNA sequencing dataset was downloaded from TCGA, survival analysis was used to evaluate the prognostic value of PVT1 in sarcoma. The potential mechan ...[more]

PMID: 31598169

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Project description:Objective: This study aimed to investigate the correlation of long noncoding RNA plasmacytoma variant translocation 1 with clinical features and prognosis in patients with multiple myeloma. Methods: The bone marrow samples were collected from 128 patients with de novo symptomatic multiple myeloma (before initial treatment) and 30 healthy donors (on the enrollment). Long noncoding RNA plasmacytoma variant translocation 1 expression in bone marrow-derived plasma cells was detected by reverse transcription quantitative polymerase chain reaction. In patients with multiple myeloma, their demographics and clinical features before treatment were collected; induction treatment response (complete response and overall response rate) and survival profiles (progression-free survival and overall survival) were assessed. Results: Expression of long noncoding RNA plasmacytoma variant translocation 1 was increased in patients with multiple myeloma compared to healthy donors. Receiver-operating characteristic curve showed that long noncoding RNA plasmacytoma variant translocation 1 distinguished patients with multiple myeloma from healthy donors with an area under the curve of 0.884 (95% confidence interval: 0.829-0.940). In patients with multiple myeloma, high expression of long noncoding RNA plasmacytoma variant translocation 1 correlated with elevated β-2 microglobulin, increased International Staging System stage, and raised Del (17p), but it did not correlate with other biochemical indexes or chromosomal abnormalities. Furthermore, long noncoding RNA plasmacytoma variant translocation 1 high expression patients presented with decreased complete response and overall response rate compared to long noncoding RNA plasmacytoma variant translocation 1 low expression patients, and high expression of long noncoding RNA plasmacytoma variant translocation 1 predicted unfavorable progression-free survival as well overall survival in patients with multiple myeloma. Conclusion: Long noncoding RNA plasmacytoma variant translocation 1 might be a potential biomarker for the supervision of disease progression and prognosis in patients with multiple myeloma.

Project description:The current study aimed to identify the potential clinical significance and molecular mechanisms of kinesin (KIF) family member genes in lung adenocarcinoma (LUAD) using genome‑wide RNA sequencing (RNA‑seq) datasets derived from The Cancer Genome Atlas (TCGA) database. Clinical parameters and RNA‑seq data of patients with LUAD from the TCGA database enabled the assessment of the clinical significance of KIF genes, while the potential mechanisms of their interactions in LUAD were investigated by gene set enrichment analysis (GSEA). A gene signature with potential prognostic value was constructed via a stepwise multivariable Cox analysis. In total, 23 KIF genes were identified to be differentially expressed genes (DEGs) between the LUAD tumor and adjacent non‑cancerous tissues. Of these, 8 differentially expressed KIF genes were strongly found to be strongly associated with the overall survival of patients with LUAD. Three of these genes were found to be able to be grouped as a potential prognostic gene signature. Patients with higher risk scores calculated using this gene signature were found to have a markedly higher risk of mortality (adjusted P=0.003; adjusted HR, 1.576; 95% CI, 1.166‑2.129). Time‑dependent receiver operating characteristic analysis indicated that this prognostic signature was able to accurately predict patient prognosis with an area under curve of 0.636, 0.643,0.665, 0.670 and 0.593 for the 1‑, 2‑, 3‑, 4‑ and 5‑year survival, respectively. This prognostic gene signature was identified as an independent risk factor for LUAD and was able to more accurately predict prognosis in comparison to other known clinical parameters, as shown via comprehensive survival analysis. GSEA enrichment revealed that that KIF14, KIF18B and KIF20A mediated basic cell physiology through the regulation of the cell cycle, DNA replication, and DNA repair biological processes and pathways. On the whole, the findings of this study identified 23 KIF genes that were DEGs between LUAD tumor and adjacent non‑cancerous tissues. In total, 8 of these genes had the potential to function as prognostic and diagnostic biomarkers in patients with LUAD.

Dataset Information

Comprehensive investigation of the clinical significance and molecular mechanisms of plasmacytoma variant translocation 1 in sarcoma using genome-wide RNA sequencing data.

Publications

Comprehensive investigation of the clinical significance and molecular mechanisms of plasmacytoma variant translocation 1 in sarcoma using genome-wide RNA sequencing data.

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