Scholarlink

Background <p>Pancreatic ductal adenocarcinoma (PDAC) is a malignant form of cancer with the worst survival rate and an extremely low rate of response to treatments. The development and molecular characterization of pancreatic cancer cell lines (PCCLs) are essential for studying the biology of highly aggressive pancreatic adenocarcinoma.</p> Methods <p>We applied whole exome sequencing (WES) and RNA-seq to identify molecular characteristics of 26 newly established PCCLs. Eighteen clinically relevant anti-cancer drugs were used to assess highly heterogeneous drug responses across the 26 cell lines.</p> Results <p>We confirmed that common driver mutations of PDAC were well retained in our cell lines through WES analysis. Transcriptomic analysis identified two representative clusters that correlated with responses to certain drugs. By using Moffitt’s classification method, the two clusters, C1 and C2, showed comparable expression patterns to “Basal-like” and “Classical” types, respectively. Drug screening results showed varying responses among different cell lines. In our cohort, C2 displayed greater sensitivity to anti-cancer drugs compared to C1. Furthermore, drugs targeting similar molecular pathways exhibited corresponding reactions among cell lines.</p> Conclusions <p>Our results underscored that transcriptomic features of pancreatic cancer correlate with drug sensitivity rather than with the effects of targeted drugs. Cell lines are useful in vitro model systems for studying the molecular mechanisms of PDAC.</p> Graphical Abstract <p></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

Comprehensive molecular analysis of 26 newly established human pancreatic ductal adenocarcinoma cell lines reveals two clusters with variating drug sensitivities

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月19日

查看全文
  • Ju Eun Maeng,
  • Jae-Hyeon Kim,
  • Soon-Chan Kim,
  • Won-Gun Yun,
  • Wooil Kwon,
  • Youngmin Han,
  • Do-Youn Oh,
  • Sang Hyub Lee,
  • Jin-Young Jang,
  • Ja-Lok Ku

摘要

Background

Pancreatic ductal adenocarcinoma (PDAC) is a malignant form of cancer with the worst survival rate and an extremely low rate of response to treatments. The development and molecular characterization of pancreatic cancer cell lines (PCCLs) are essential for studying the biology of highly aggressive pancreatic adenocarcinoma.

Methods

We applied whole exome sequencing (WES) and RNA-seq to identify molecular characteristics of 26 newly established PCCLs. Eighteen clinically relevant anti-cancer drugs were used to assess highly heterogeneous drug responses across the 26 cell lines.

Results

We confirmed that common driver mutations of PDAC were well retained in our cell lines through WES analysis. Transcriptomic analysis identified two representative clusters that correlated with responses to certain drugs. By using Moffitt’s classification method, the two clusters, C1 and C2, showed comparable expression patterns to “Basal-like” and “Classical” types, respectively. Drug screening results showed varying responses among different cell lines. In our cohort, C2 displayed greater sensitivity to anti-cancer drugs compared to C1. Furthermore, drugs targeting similar molecular pathways exhibited corresponding reactions among cell lines.

Conclusions

Our results underscored that transcriptomic features of pancreatic cancer correlate with drug sensitivity rather than with the effects of targeted drugs. Cell lines are useful in vitro model systems for studying the molecular mechanisms of PDAC.

Graphical Abstract