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pmid:39361158

Identification of key genes participating in copper-diethyldithiocarbamate-related cell death process and predicting the development of prostate cancer.

Xin'an Wang · Chengdang Xu · Junjie Ma · Xiao Wang · Xi Chen

Discover oncology · 2024 doi:10.1007/s12672-024-01390-6

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:39361158
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science-record
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paper object · 10 fields
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title
Identification of key genes participating in copper-diethyldithiocarbamate-related cell death process and predicting the development of prostate cancer.
doi
10.1007/s12672-024-01390-6
pmid
39361158
authors array · 5 items
[0]
Xin'an Wang
[1]
Chengdang Xu
[2]
Junjie Ma
[3]
Xiao Wang
[4]
Xi Chen
journal
Discover oncology
year
2024
abstract
Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.
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Lasso regression model was used to estimate the roles of these genes in affecting the prognosis of patients with PCa.
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sections[7] "Survival analysis" paragraph 2
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Lasso regression model was used to estimate the roles of these genes in affecting the prognosis of patients with PCa.
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The data from public databases can be acquired from TCGA (http://portal.gdc.cancer.gov), GEO (https://www.ncbi.nlm.nih.gov/gds), and CPGEA (http://www.cpgea.com/) databases. Other data can get from the corresponding author.
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sections[31] "Data availability" paragraph 2
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The data from public databases can be acquired from TCGA (http://portal.gdc.cancer.gov), GEO (https://www.ncbi.nlm.nih.gov/gds), and CPGEA (http://www.cpgea.com/) databases. Other data can get from the corresponding author.
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The lasso regression model identified five Cu-DDC-related cell death genes whose combined expression significantly influenced patients’ disease-free survival in PCa (P = 1.1e-06).
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We found that these genes effectively influenced the DFS in patients with PCa with a P = 1.1e-06 (Fig. 4C).
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sections[20] "Prognostic value of Cu-DDC-related cell death genes in PCa" paragraph 2
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Using microarray and clinical data from the TCGA database, we constructed a lasso regression model, wherein we found that these genes affected the patients’ DFS status.
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sections[20] "Prognostic value of Cu-DDC-related cell death genes in PCa" paragraph 2
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We found that these genes effectively influenced the DFS in patients with PCa with a P = 1.1e-06 (Fig. 4C).
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The lasso regression model identified five Cu-DDC-related cell death genes whose combined expression significantly influenced patients’ disease-free survival in PCa (P = 1.1e-06).
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Materials and methods Cell culture and transfection LNCaP PCa cell line was purchased from the C
[1]
Bank (Shanghai, China). The cell culture and transfection process was carried out as previous study de
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Complete file
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Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients' disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.", "claims": [{"id": "claim-method", "statement": "Lasso regression model was used to estimate the roles of these genes in affecting the prognosis of patients with PCa.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39361158", "locator": "sections[7] \"Survival analysis\" paragraph 2", "quote": "Lasso regression model was used to estimate the roles of these genes in affecting the prognosis of patients with PCa."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data from public databases can be acquired from TCGA (http://portal.gdc.cancer.gov), GEO (https://www.ncbi.nlm.nih.gov/gds), and CPGEA (http://www.cpgea.com/) databases. 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