Scholarlink

Background <p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with drug resistance significantly impeding effective chemotherapy. The clinical importance of key genes in PDAC chemoresistance remains unclear.</p> Methods <p>Cytotoxicity assays were conducted on eight PDAC cell lines treated with gemcitabine, albumin paclitaxel, irinotecan, 5-FU, and cis-platinum. Based on GR50 values, cell lines were categorized as chemosensitive (CS) or chemoresistant (CR). RNA-seq data from the Cancer Cell Line Encyclopedia were analyzed for differential gene expression. Various statistical methods, including univariate Cox, LASSO, random forest, and multivariate Cox regression, were employed to construct a risk signature. This model’s effectiveness was validated using time-dependent ROC curves and Kaplan–Meier survival analysis in TCGA and GSE57495 + GSE28735 combined datasets. Downstream molecules of core genes were explored, and the core gene’s function was validated through in vivo and in vitro experiments.</p> Results <p>Drug resistance profiles were established based on GR50 values. EDC4 and USP20 were identified as key genes in the risk signature. qRT-PCR validated core gene expressions in PDAC cell lines. EDC4 was selected for further analysis due to its highest correlation coefficient in the multivariate Cox regression model. EDC4 knockdown increased proliferation and chemoresistance in MIA PaCa-2 cells, while overexpression inhibited these traits in AsPC-1 cells. MATN3 and SGCE were identified as downstream targets of EDC4. Immunohistochemistry of tissue microarrays confirmed that low EDC4 levels were associated with poor prognosis in PDAC, highlighting its potential as a therapeutic target.</p> Conclusion <p>PDAC cell lines exhibit distinct chemoresistance capabilities. EDC4 and its downstream targets MATN3 and SGCE play significant roles in PDAC multidrug chemoresistance, providing novel insights for treatment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

EDC4 enhances multi-drug chemosensitivity in pancreatic cancer via GR50-based profiling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

查看全文
  • Cheng Qin,
  • Tianyu Li,
  • Bangbo Zhao,
  • Zeru Li,
  • Yutong Zhao,
  • Xiangyu Zhang,
  • Yiping Xie,
  • Yutong Yan,
  • Jiashu Han,
  • Qianqian Shao,
  • Chen Lin,
  • Weibin Wang

摘要

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with drug resistance significantly impeding effective chemotherapy. The clinical importance of key genes in PDAC chemoresistance remains unclear.

Methods

Cytotoxicity assays were conducted on eight PDAC cell lines treated with gemcitabine, albumin paclitaxel, irinotecan, 5-FU, and cis-platinum. Based on GR50 values, cell lines were categorized as chemosensitive (CS) or chemoresistant (CR). RNA-seq data from the Cancer Cell Line Encyclopedia were analyzed for differential gene expression. Various statistical methods, including univariate Cox, LASSO, random forest, and multivariate Cox regression, were employed to construct a risk signature. This model’s effectiveness was validated using time-dependent ROC curves and Kaplan–Meier survival analysis in TCGA and GSE57495 + GSE28735 combined datasets. Downstream molecules of core genes were explored, and the core gene’s function was validated through in vivo and in vitro experiments.

Results

Drug resistance profiles were established based on GR50 values. EDC4 and USP20 were identified as key genes in the risk signature. qRT-PCR validated core gene expressions in PDAC cell lines. EDC4 was selected for further analysis due to its highest correlation coefficient in the multivariate Cox regression model. EDC4 knockdown increased proliferation and chemoresistance in MIA PaCa-2 cells, while overexpression inhibited these traits in AsPC-1 cells. MATN3 and SGCE were identified as downstream targets of EDC4. Immunohistochemistry of tissue microarrays confirmed that low EDC4 levels were associated with poor prognosis in PDAC, highlighting its potential as a therapeutic target.

Conclusion

PDAC cell lines exhibit distinct chemoresistance capabilities. EDC4 and its downstream targets MATN3 and SGCE play significant roles in PDAC multidrug chemoresistance, providing novel insights for treatment.