Profiling Heterogeneous Circulating Tumor Cells (CTC) Populations in Pancreatic Cancer Using a Serial Microfluidic...

Area of Science:

• Oncology
• Biotechnology
• Genomics

Background:

• Epithelial cellular adhesion molecule (EpCAM)-only assays limit circulating tumor cell (CTC) utility in pancreatic cancer.
• Heterogeneous CTC populations, including epithelial (EpC) and epithelial-to-mesenchymal transition (EMT)-like (EMTC) cells, are crucial for understanding pancreatic cancer biology.
• Current methods struggle to capture the full spectrum of CTCs in pancreatic adenocarcinoma.

Purpose of the Study:

• To develop and validate an integrated technology- and biology-based approach for isolating heterogeneous CTCs from pancreatic cancer patients.
• To simultaneously isolate both EpCs and EMTCs from whole blood using a microfluidic 'Carpet Chip'.
• To investigate the clinical relevance and genetic profiles of distinct CTC populations in relation to pancreatic cancer progression.

Main Methods:

• Utilized a microfluidic 'Carpet Chip' for simultaneous isolation of EpCs and EMTCs by targeting EpCAM and CD133 surface markers.
• Assessed recovery and purity of cancer cell lines spiked into whole blood (≥97% recovery, >76% purity).
• Performed gene expression profiling on isolated CTCs from 17 patients.

Main Results:

• Successfully isolated both EpCs and EMTCs from 35 pancreatic cancer patients.
• Observed significantly higher numbers of EMTCs than EpCs, correlating with pancreatic cancer's aggressive nature.
• Found higher EMTC counts in patients with lymph node involvement and identified specific upregulated genes (CXCR1 in EpCs, POU5F1/Oct-4 and MYC in EMTCs).

Conclusions:

• Demonstrated successful isolation and genomic profiling of heterogeneous CTC populations in pancreatic cancer.
• Identified distinct genetic signatures in EpCs and EMTCs, providing insights into pancreatic cancer aggressiveness and patient outcomes.
• The 'Carpet Chip' approach offers a promising tool for studying CTC heterogeneity and its clinical relevance in pancreatic adenocarcinoma.