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pmid:37701108

Novel potential urinary biomarkers for effective diagnosis and prognostic evaluation of high-grade bladder cancer.

Zhi-Guo Zhang · Zhen-Duo Shi · Jia-Jun Dong · Yu-Ang Chen · Ming-Yang Cao · Yun-Tian Li · Wei-Ming Ma · Lin Hao · Kun Pang · Jia-He Zhou · Wen-Da Zhang · Yang Dong · Cong-Hui Han

Translational cancer research · 2023 doi:10.21037/tcr-23-98

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Novel potential urinary biomarkers for effective diagnosis and prognostic evaluation of high-grade bladder cancer.
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10.21037/tcr-23-98
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37701108
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Zhi-Guo Zhang
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Zhen-Duo Shi
[2]
Jia-Jun Dong
[3]
Yu-Ang Chen
[4]
Ming-Yang Cao
[5]
Yun-Tian Li
[6]
Wei-Ming Ma
[7]
Lin Hao
[8]
Kun Pang
[9]
Jia-He Zhou
[10]
Wen-Da Zhang
[11]
Yang Dong
[12]
Cong-Hui Han
journal
Translational cancer research
year
2023
abstract
Background: High-grade bladder cancer (HGBC) has a higher malignant potential, recurrence and progression rate compared to low-grade phenotype. Its early symptoms are often vague, making non-invasive diagnosis using urinary biomarkers a promising approach. Methods: The gene expression data from urine samples of patients with HGBC was extracted from the GSE68020 dataset. The clinical information and gene expression data in tumor tissues of HGBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Multivariate Cox analysis was used to predict the optimal risk model. The protein-protein interaction (PPI) analysis was performed via the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Overall survival (OS) was evaluated in the Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Competing endogenous RNA (ceRNA) network was also visualized using Cytoscape. The expression levels of specific genes were assessed through quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, co-expressed genes and potential biological functions related to specific genes were explored based on the Cancer Cell Line Encyclopedia (CCLE) database. Results: A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones. Using these urinary DEGs and the clinical information of HGBC patients, we developed an optimal risk model consisting of eight genes to predict the patient outcome. By integrating the node degree values in the PPI network with the expression changes in both urine and tissue samples, eighteen hub genes were selected out. Among them, DKC1 and SNRPG had the most prominent comprehensive values, and EFTUD2, LOR and EBNA1BP2 were relevant to a worse OS in bladder cancer patients. The ceRNA network of hub genes indicated that DKC1 may be directly regulated by miR-150 in HGBC. The upregulation of both SNRPG and DKC1 were detected in HGBC cells, which were also observed in various tumor tissues and malignant cell lines, displaying high correlations with other hub genes. Conclusions: Our study may provide theoretical basis for the development of effective non-invasive detection and treatment strategies, and further research is necessary to explore the clinical applications of these findings.
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Its early symptoms are often vague, making non-invasive diagnosis using urinary biomarkers a promising approach.\nMethods: The gene expression data from urine samples of patients with HGBC was extracted from the GSE68020 dataset. The clinical information and gene expression data in tumor tissues of HGBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Multivariate Cox analysis was used to predict the optimal risk model. The protein-protein interaction (PPI) analysis was performed via the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Overall survival (OS) was evaluated in the Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Competing endogenous RNA (ceRNA) network was also visualized using Cytoscape. The expression levels of specific genes were assessed through quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, co-expressed genes and potential biological functions related to specific genes were explored based on the Cancer Cell Line Encyclopedia (CCLE) database.\nResults: A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones. Using these urinary DEGs and the clinical information of HGBC patients, we developed an optimal risk model consisting of eight genes to predict the patient outcome. By integrating the node degree values in the PPI network with the expression changes in both urine and tissue samples, eighteen hub genes were selected out. Among them, DKC1 and SNRPG had the most prominent comprehensive values, and EFTUD2, LOR and EBNA1BP2 were relevant to a worse OS in bladder cancer patients. The ceRNA network of hub genes indicated that DKC1 may be directly regulated by miR-150 in HGBC. The upregulation of both SNRPG and DKC1 were detected in HGBC cells, which were also observed in various tumor tissues and malignant cell lines, displaying high correlations with other hub genes.\nConclusions: Our study may provide theoretical basis for the development of effective non-invasive detection and treatment strategies, and further research is necessary to explore the clinical applications of these findings.", "claims": [{"id": "claim-method", "statement": "The DEGs were screened using the Linear Models for Microarray Analysis package (13) with cut off criteria of |logFC (fold change)| ≥0.5 and P value <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37701108", "locator": "sections[5] \"Data preprocessing and identification of DEGs\" paragraph 2", "quote": "The DEGs were screened using the Linear Models for Microarray Analysis package (13) with cut off criteria of |logFC (fold change)| ≥0.5 and P value <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE68020 dataset and its corresponding platform annotation files were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo) (8), which contained of the data of 50 urine sediment samples, including 30 HGBC and 20 benign samples assessed using urine cytology.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37701108", "locator": "sections[4] \"Data mining and collection\" paragraph 2", "quote": "GSE68020 dataset and its corresponding platform annotation files were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo) (8), which contained of the data of 50 urine sediment samples, including 30 HGBC and 20 benign samples assessed using urine cytology."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 560 differentially expressed genes in urine sediment samples from high-grade bladder cancer patients compared with benign samples.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37701108", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 560 differentially expressed genes in urine sediment samples from high-grade bladder cancer patients compared with benign samples.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37701108"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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