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Published on: December 26, 2016
Identifying potential anti-metastasis drugs for prostate cancer through integrative bioinformatics analysis and
Zhi Wei Li1, Jiang Fan Yu2, Feng Han3
1Department of Urology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Background:
Metastasis poses the greatest threat to the lives of individuals with prostate cancer. Therefore, it is imperative to identify the underlying mechanism driving metastasis. Doing so would facilitate the detection of new diagnostic biomarkers and the advancement of treatment options for patients.
Methods:
Metastasis-related modules were identified through weighted gene co-expression network analysis based on microarray GSE6919. Hub genes were confirmed by quantitative real-time PCR across different prostate cell lines and clinic samples. Pivotal genes were determined through integration of RNA and transcription factor-target associated interactions. To predict drugs with potential to suppress tumor metastasis, we applied molecular networks using the DrugBank database. Drug repositioning analysis and confirmation of drug screen were conducted using the compound library. Confirmation of selective cytotoxicity of cupric oxide was carried out via invasion, transwell and apoptosis assays.
Results:
We identified five metastasis-related modules. Of these modules, two were identified to represent core dysfunction modules in which five hub genes were determined for each module. Five of these 10 genes correlating with prostate cancer progression. Furthermore, our analysis revealed that there are 36 drugs with the potential to be active against tumor metastasis. Finally, we identified four compounds that have not previously been reported to have any association with cancer therapy. Of these, cupric oxide was determined to have the best chemotherapeutic potential in treating prostate cancer metastasis.
Conclusions:
By combining bioinformatics methods with compound library screening, this study proposes a valuable approach to drug discovery. Cupric oxide showed the potential in the treatment of prostate cancer metastasis and deserves further study.
Insights
This study identifies key genes and drugs targeting prostate cancer metastasis. Cupric oxide shows significant potential as a novel therapeutic agent for treating metastatic prostate cancer.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- Prostate cancer metastasis is a primary cause of mortality.
- Understanding metastasis mechanisms is crucial for developing new therapies and biomarkers.
- Identifying drivers of metastasis can improve patient outcomes.
Purpose of the Study:
- To identify metastasis-related genes and drug candidates for prostate cancer.
- To investigate the therapeutic potential of identified compounds against prostate cancer metastasis.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) for metastasis modules.
- Quantitative real-time PCR for hub gene validation.
- Integration of RNA and transcription factor interactions.
- Drug repositioning using molecular networks and compound library screening.
- Cytotoxicity assays for cupric oxide evaluation.
Main Results:
- Identified five metastasis-related modules and 10 hub genes, with five linked to prostate cancer progression.
- Discovered 36 potential anti-metastasis drugs.
- Identified four novel compounds for cancer therapy, including cupric oxide.
- Cupric oxide demonstrated significant chemotherapeutic potential against prostate cancer metastasis.
Conclusions:
- Combined bioinformatics and screening offer a robust drug discovery approach.
- Cupric oxide exhibits promising therapeutic potential for prostate cancer metastasis.
- Further research into cupric oxide for prostate cancer treatment is warranted.
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