45: Peritoneal Lavage Exosomes Differential Gene Expression is Associated with Response to Intraperitoneal Chemotherapy in Patients with Gastric Carcinomatosis - Results from a Phase II Clinical Trial (STOPGAP)

Monday, February 19, 2024

9:50 AM - 10:00 AM AST

Location: Miramar I & II

Abstract Presenter(s)

Maheswari Senthil, MD (she/her/hers)

Chief of Surgical Oncology
University of California, Irvine
Irvine, California, United States

Submitter(s)

Maheswari Senthil, MD (she/her/hers)

Chief of Surgical Oncology
University of California, Irvine
Irvine, California, United States

Author(s)

Maheswari Senthil, MD (she/her/hers)

Chief of Surgical Oncology
University of California, Irvine
Irvine, California, United States
VR

Vinodh Radhakrishnan, PhD

Project Scientist
University of California Irvine, United States
FT

Fatemeh Tajik, MD

Research Associate
University of California Irvine, United States
Shaina Sedighim, MD

Resident Physician
University of California, Irvine, Department of Surgery
Irvine, California, United States
Oliver Eng, MD (he/him/his)

Associate Professor of Surgery
University of California, Irvine
Orange, California, United States
Shishir K. Maithel, MD, FACS

Professor, Department of Surgery
Winship Cancer Institute of Emory University
Atlanta, GA, United States
NU

Nataliya V. Uboha, MD, PhD

Associate Professor
University of Wisconsin, United States
FD

Farshid Dayyani, MD, PhD

Professor of Medicine
University of California Irvine, United States

Disclosure(s):

Shaina Sedighim, MD: No financial relationships to disclose

Oliver Eng, MD: Tempus Labs, Inc.: Speaker (Ongoing)

Introduction: Exosome gene expression can provide valuable insights into cancer biology and serve as predictive biomarkers. STOPGAP is an ongoing, phase II single-arm clinical trial of normothermic intraperitoneal chemotherapy (NIPEC) with paclitaxel (PTX) combined with systemic therapy in patients with gastric peritoneal carcinomatosis (PC) (NCT 04762953). We conducted exosome differential gene expression analysis of peritoneal lavage fluid pre- and post- intraperitoneal (IP) PTX to identify gene expression patterns associated with treatment response.

Methods: Patients enrolled in the STOPGAP study underwent diagnostic laparoscopy pre- and post IP PTX during which peritoneal lavage samples were obtained. Exosomes were isolated from lavage fluid and confirmed with nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM). Exosome RNA was extracted and analyzed utilizing NanoString’s PanCancer Progression Panel (770 genes). Differential gene expression between pre- and post IP PTX was performed with log2 fold expression change cutoff of ≥1.5 to ≤ -1.5 with p-Value of ≤ 0.05.

Results: Pre-and post IP PTX peritoneal lavage samples (n=11) from five patients were included in the study. All patients had poorly differentiated diffuse type gastric cancer with either PC (n=4) or cyt+(n=1) disease; median age is 48, and 60% are female. All five patients had treatment response. The median PCI pre-and post-IP were 13(0-36) and 8(0-30) respectively, representing an average of 38.4% reduction in the PCI. 3/5 (66%) patients underwent cytoreduction surgery. NTA confirmed the isolated extracellular vesicles are exosomes with average size of 108.1 nm ( SD± 0.8 nm) and TEM revealed round morphology (Figure1a and b). Eight genes were highly differentially expressed (DEGs) in the post-IP PTX group compared to pre-IP (Figure 1c). COL3A1, OGN were upregulated and AKT, SERPINH1, FGFR4, CD46, MAP3K7 and VHL were downregulated (p < 0.05). The functions of the DEGs are associated with collagen remodeling, cellular growth, epithelial-mesenchymal transition, angiogenesis, and cancer progression.

Conclusions: Peritoneal lavage exosome differential gene expression is associated with treatment response in patients with gastric PC treated with NIPEC PTX. The functions of the DEGs may offer valuable insights into the biologic changes associated with treatment response in PC. We plan to expand this work with additional patients enrolled in STOPGAP.

Learning Objectives:

describe the role of exosomes in gastric cancer
describe the genes that are downregulated and upregulated in peritoneal lavage exosomes with normothermic intraperitoneal chemotherapy in gastric carcinomatosis
describe the functions of differentially expressed genes associated with treatment response in gastric carcinomatosis