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<p>Gene expression profiling in precision oncology is increasing with uncertain validity across platforms. In this study, we examined the application of PurIST, a molecular subtyping algorithm for pancreatic ductal adenocarcinoma (PDAC), across different platforms. We compared PurIST calls between matched samples processed by whole transcriptome and commercial exome capture RNA-seq. In parallel, we compared subtypes between matched samples processed by NanoString and whole transcriptome RNA-seq from the PANCREAS trial (NCT04683315). Between whole transcriptome and exome capture, subtype agreement was 81% with significant increase in basal-like subtype with exome capture. Differences in overall survival in patients with basal-like tumors compared to classical tumors did not reach statistical significance using exome capture (log-rank <i>P</i> = 0.061), whereas with whole transcriptome it was significantly shorter (log-rank <i>P</i> &lt; 0.0001). Subtype agreement between whole transcriptome RNA-seq and NanoString was higher at 95%. PurIST results should be interpreted with caution when using exome capture methods.</p>

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Cross-platform comparison of gene expression-based cancer molecular subtyping reveals discrepancies with exome capture methods

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月20日

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  • Jaewon J. Lee,
  • Mohammed Aldakkak,
  • Ashley B. Morrison,
  • Sam Z. Thalji,
  • Xianlu L. Peng,
  • Yan Li,
  • Margaret L. Gulley,
  • Erkut H. Borazanci,
  • Susan Tsai,
  • Naim U. Rashid,
  • Jen Jen Yeh

摘要

Gene expression profiling in precision oncology is increasing with uncertain validity across platforms. In this study, we examined the application of PurIST, a molecular subtyping algorithm for pancreatic ductal adenocarcinoma (PDAC), across different platforms. We compared PurIST calls between matched samples processed by whole transcriptome and commercial exome capture RNA-seq. In parallel, we compared subtypes between matched samples processed by NanoString and whole transcriptome RNA-seq from the PANCREAS trial (NCT04683315). Between whole transcriptome and exome capture, subtype agreement was 81% with significant increase in basal-like subtype with exome capture. Differences in overall survival in patients with basal-like tumors compared to classical tumors did not reach statistical significance using exome capture (log-rank P = 0.061), whereas with whole transcriptome it was significantly shorter (log-rank P < 0.0001). Subtype agreement between whole transcriptome RNA-seq and NanoString was higher at 95%. PurIST results should be interpreted with caution when using exome capture methods.