Cancer-related cells and oncosomes in the liquid biopsy of pancreatic cancer patients undergoing surgery

Stephanie N Shishido; Emmeline Lin; Nicholas Nissen; George Courcoubetis; Divya Suresh; Jeremy Mason; Arsen Osipov; Andrew E Hendifar; Michael Lewis; Srinivas Gaddam; Stephen Pandol; Peter Kuhn; Simon K Lo

doi:10.1038/s41698-024-00521-0

Cancer-related cells and oncosomes in the liquid biopsy of pancreatic cancer patients undergoing surgery

NPJ Precis Oncol. 2024 Feb 15;8(1):36. doi: 10.1038/s41698-024-00521-0.

Authors

Stephanie N Shishido^#¹, Emmeline Lin^#¹, Nicholas Nissen², George Courcoubetis¹, Divya Suresh¹, Jeremy Mason^{1

3

4}, Arsen Osipov⁵, Andrew E Hendifar⁵, Michael Lewis^{2

6

7}, Srinivas Gaddam², Stephen Pandol², Peter Kuhn^{8

9

10

11

12

13}, Simon K Lo¹⁴

Affiliations

¹ Convergent Science Institute for Cancer, Michelson Center, University of Southern California, Los Angeles, CA, 90089, USA.
² Pancreatic and Biliary Diseases Program, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA.
³ Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁴ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁵ IM Hematology Oncology, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA.
⁶ Greater Los Angeles Veterans Affairs System, Los Angeles, CA, 90073, USA.
⁷ Clark Atlanta University, Center for Cancer Research and Therapeutic Development, Atlanta, GA, 30314, USA.
⁸ Convergent Science Institute for Cancer, Michelson Center, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
⁹ Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. pkuhn@usc.edu.
¹⁰ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. pkuhn@usc.edu.
¹¹ Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
¹² Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
¹³ Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, 90089, USA. pkuhn@usc.edu.
¹⁴ Pancreatic and Biliary Diseases Program, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA. simon.lo@cshs.org.

^# Contributed equally.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 10% due to its late diagnosis, rapid metastasis, and chemotherapeutic resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival but the effect of surgery on disease dissemination is unknown. The primary objective of this study was to characterize cellular and acellular blood-based analytes in portal and peripheral blood before pancreatic manipulation, during tumor dissection and immediately after surgical resection to determine the effects of the surgery. This study used the non-enriching third generation High-Definition Single Cell Assay (HDSCA3.0) workflow to investigate heterogeneous circulating rare cell population in the blood. Blood from both sites taken before surgical manipulation of the pancreas had significantly greater incidence of total rare cellular and acellular analytes than normal donor samples. Post-surgery portal and peripheral blood had significantly greater incidence of specific cellular and acellular subtypes compared to the matched pre- and during-surgery samples. Our results reveal that in patients with PDAC liquid biopsy analytes are increased in both the portal and peripheral blood; portal blood contains a higher frequency of analytes than in the peripheral blood; total analytes in the portal and peripheral blood samples were significantly associated with the tumor volume and pathological T stage; and the surgical procedure increased the blood levels of circulating cellular and acellular analytes, but not Epi.CTCs or Mes.CTCs. This study demonstrates liquid biopsy's utility in monitoring patients with PDAC with surgically resectable disease.

Grants and funding

P30 CA014089/CA/NCI NIH HHS/United States