Abstract 3320: Liquid biopsy to detect biomarkers in early-stage surgically-resected pancreatic cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.3320-3320
• Main Authors: Lin, Emmeline Y., Courcoubetis, George, Suresh, Divya, Mason, Jeremy, Pandol, Stephen J., Lo, Simon, Nissen, Nicholas, Gaddam, Srinivas, Kuhn, Peter, Shishido, Stephanie N.
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-3320

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a five-year survival rate of around 7% due to its late diagnosis, rapid metastasis, and chemotherapy resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival (5-year rate of 20%). Given the clinical challenges and the need for personalized care strategies to maximize patient survival, we propose the utility of the minimally invasive liquid biopsy to identify circulating biomarkers in patient blood to guide prognosis and monitor treatment. This study used the non-enriching third generation High-Definition Single Cell Assay (HDSCA3.0) workflow to investigate the clinical significance of a heterogeneous circulating rare cell population in both the peripheral and portal vein blood of early-stage PDAC patients (n = 20) at four different time points—pre-, during, and post- surgical resection, as well as at one-week follow-up. Compared to normal donor samples (n = 50), PDAC patients had a significantly greater incidence of circulating tumor cells (CTCs: cytokeratin-positive (CK+) and CD35/45-negative). There was no significant difference in rare cell incidence between peripheral and portal vein samples. However, specific phenotypes of rare cells were observed at different frequencies based on time of sample collection. Patient samples collected pre-surgery had a significantly higher incidence of CTCs than samples collected during surgery, while post-surgery samples had a significantly higher incidence of total CK+ rare cells and mesenchymal CTCs (Vimentin-positive, CK+) than during-surgery samples. While post-surgical samples also had a higher total CK+ rare cell and CTC incidence than pre-surgical samples, the difference was not statistically significant. Additionally, patients who received neoadjuvant therapy with surgical resection had lower average incidence of rare cells. Overall, the data presented here reveal that 1) liquid biopsy analytes are detected at a higher incidence in localized PDAC than normal donors; 2) the time point of sample collection in relation to surgery leads to a statistically significant different in frequency of detectable analytes; and 3) anatomical location of blood draw is not associated with difference in rare cell incidence. This study demonstrates the liquid biopsy’s utility in early-stage PDAC detection at the time of surgical resection. Citation Format: Emmeline Y.