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Abstract：
BACKGROUND: To identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.
METHODS: Gene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays.
RESULTS: Results showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified.
CONCLUSIONS: This study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.
METHODS: Gene expression profiles were retrieved from the GEO database. DEGs were identified by comparing gene expression profiles between cisplatin-sensitive and resistant ovarian cancer cell lines. The identified genes were further subjected to GO, KEGG, and PPI network analysis. Potential inhibitors of key genes were identified through methods such as LibDock nuclear molecular docking. In vitro assays and RT-qPCR were performed to assess the expression levels of key genes in ovarian cancer cell lines. The sensitivity of cells to chemotherapy and proliferation of key gene knockout cells were evaluated through CCK8 and Clonogenic assays.
RESULTS: Results showed that 12 genes influenced the chemosensitivity of the ovarian cancer cell line SKOV3, and 9 genes were associated with the prognosis and survival outcomes of ovarian cancer patients. RT-qPCR results revealed NDRG1, CYBRD1, MT2A, CNIH3, DPYSL3, and CARMIL1 were upregulated, whereas ERBB4, ANK3, B2M, LRRTM4, EYA4, and SLIT2 were downregulated in cisplatin-resistant cell lines. NDRG1, CYBRD1, and DPYSL3 knock-down significantly inhibited the proliferation of cisplatin-resistant cell line SKOV3. Finally, photofrin, a small-molecule compound targeting CYBRD1, was identified.
CONCLUSIONS: This study reveals changes in the expression level of some genes associated with cisplatin-resistant ovarian cancer. In addition, a new small molecule compound was identified for the treatment of cisplatin-resistant ovarian cancer.
摘要：
背景：为了确定与卵巢癌顺铂耐药相关的关键基因，对GEO数据库中的三个数据集进行了综合分析，并通过实验验证。
方法：从GEO数据库检索基因表达谱。通过比较顺铂敏感和耐药卵巢癌细胞系之间的基因表达谱来鉴定DEGs。鉴定的基因进一步进行GO，KEGG,和PPI网络分析。通过诸如LibDock核分子对接的方法鉴定了关键基因的潜在抑制剂。进行体外测定和RT-qPCR以评估卵巢癌细胞系中关键基因的表达水平。通过CCK8和克隆形成试验评价细胞对化疗的敏感性和关键基因敲除细胞的增殖。
结果：结果显示12个基因影响卵巢癌细胞株SKOV3的化疗敏感性，9个基因与卵巢癌患者的预后和生存结局相关。RT-qPCR结果显示NDRG1、CYBRD1、MT2A、CNIH3、DPYSL3和CARMIL1上调，而ERBB4，ANK3，B2M，LRRTM4、EYA4和SLIT2在顺铂抗性细胞系中下调。NDRG1、CYBRD1和DPYSL3敲低显著抑制顺铂耐药细胞株SKOV3的增殖。最后,photofrin,鉴定出一种靶向CYBRD1的小分子化合物.
结论：本研究揭示了一些与顺铂耐药卵巢癌相关的基因表达水平的变化。此外,一种新的小分子化合物被鉴定用于治疗顺铂耐药的卵巢癌.
方法：从GEO数据库检索基因表达谱。通过比较顺铂敏感和耐药卵巢癌细胞系之间的基因表达谱来鉴定DEGs。鉴定的基因进一步进行GO，KEGG,和PPI网络分析。通过诸如LibDock核分子对接的方法鉴定了关键基因的潜在抑制剂。进行体外测定和RT-qPCR以评估卵巢癌细胞系中关键基因的表达水平。通过CCK8和克隆形成试验评价细胞对化疗的敏感性和关键基因敲除细胞的增殖。
结果：结果显示12个基因影响卵巢癌细胞株SKOV3的化疗敏感性，9个基因与卵巢癌患者的预后和生存结局相关。RT-qPCR结果显示NDRG1、CYBRD1、MT2A、CNIH3、DPYSL3和CARMIL1上调，而ERBB4，ANK3，B2M，LRRTM4、EYA4和SLIT2在顺铂抗性细胞系中下调。NDRG1、CYBRD1和DPYSL3敲低显著抑制顺铂耐药细胞株SKOV3的增殖。最后,photofrin,鉴定出一种靶向CYBRD1的小分子化合物.
结论：本研究揭示了一些与顺铂耐药卵巢癌相关的基因表达水平的变化。此外,一种新的小分子化合物被鉴定用于治疗顺铂耐药的卵巢癌.
