Abstract 5579: Increased number of EMT-like CTCs relative to epithelial CTCs reveals signatures of poor outcomes in pancreatic cancer

Objective: Although circulating tumor cells9 (CTCs) isolation from pancreatic adenocarcinoma (PaCa) patients is feasible, investigation of their clinical utility has proven less successful than other cancer types, due to poor technology sensitivity and EpCAM-only based CTC assays. Design: We present an integrated technology and biology-based approach using a microfluidic “Carpet chip” to study the biologic relevance of rare CTCs. We isolate both circulating epithelial CTCs (EpCs) and EMT-like CTCs (EMTCs) simultaneously from whole blood of PaCa patients (n=35), targeting two different surface markers: anti-EpCAM and anti-CD133. Gene expression profiling of CTCs was performed with 96 genes (n=17). Results: Recovery of cancer cell lines spiked into whole blood is ≥97% with u003e76% purity. Of the 35 PaCa patients analyzed, 34 had ≥5 EpCs/mL and 35 had ≥15 EMTCs/mL. Higher numbers of EMTCs were observed in patients with lymph node involvement (N1) compared to patients without. The ratio of EpCs to total number of CTCs marginally decreased with advanced stage, while the ratio of EMTCs increased. Gene expression profiling showed CXCR1 was significantly upregulated in EpCs whereas POU5F1/Oct-4 and MYC were upregulated in EMTCs, demonstrating inherent phenotypic differences. Early-stage patients with significantly better overall survival and/or progression-free survival showed significant higher expression of genes including ERCC1 and TTF1. Conclusions: We demonstrated successful isolation of heterogeneous population of CTCs (EpCs and EMTCs). We recovered significantly higher number of EMTCs in PaCa patients compared to EpCs, reflecting aggressive nature of PaCa. Profiling of CTCs revealed genetic signatures relevant to predicting patients9 outcomes. Citation Format: Mina Zeinali, Vasudha Murlidhar, Shamileh Fouladdel, Mathias Hafner, Shimeng Shao, Lili Zhao, Heather Cameron, Armand Iii Bankhead, Jiaqi Shi, Kyle C. Cuneo, Vaibhav Sahai, Ebrahim Azizi, Max S. Wicha, Diane M. Simeone, Sunitha Nagrath. Increased number of EMT-like CTCs relative to epithelial CTCs reveals signatures of poor outcomes in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5579.