PB0730 - Circulating activated protein C levels are reduced in cancer patients, a novel contribution to tumorigenesis?

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Julia Oto

Postdoctoral Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Co-Author(s)

Raquel Herranz, MSc

PhD Candidate
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
EP

Emma Plana

Postdoctoral Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Angiology and Vascular Surgery Service, La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
FC

Fernando Cana

Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
JA

Jose Vicente Amaya

Medical doctor
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Orthopaedics and Traumatology Service. La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
CV

Cesar D. Vera-Donoso

Medical doctor
Department of Urology, La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
MM

Manuel Martínez-Sarmiento

Medical doctor
Department of Urology, La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
SB

Santiago Bonanad

Head of Thrombosis and Hemostasis Unit
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
PM

Pilar Medina

PI
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Background: Cancer growth develops a subclinical hypercoagulable state and hypercoagulability is also a key contributor in cancer progression beyond cancer-associated thrombosis. Increasing evidence shows that coagulation proteins have multiple functions in tumor progression and metastasis, however the role of natural anticoagulants in cancer remains barely unexplored. Activated protein C (APC) displays anticoagulant and cytoprotective functions and its dysregulation may prompt cancer growth.

Aims: To ascertain whether circulating APC levels are dysregulated in cancer patients.

Methods: We obtained heparinized plasma from 88 cancer patients (45 bladder, 15 sarcoma, 9 renal and 19 prostate) and 14 controls, namely patients with a cancer suspicion anatomopathologically discarded. Circulating APC was quantified with an in-house sandwich ELISA, based on the interaction between APC and its main natural inhibitor PCI. Briefly, heparin forces APC:PCI complexation and these complexes are measured using an anti-PC primary antibody and an anti-PCI secondary antibody. Differences in circulating APC between groups was assessed with a Mann-Whitney test using GraphPad (v.8.0.1).

Results: Compared to controls, cancer patients showed a 16% reduction in circulating APC concentration (P=0.0210) (Figure 1). Attending to the different cancer types, bladder cancer patients showed a 23% APC decrease (P=0.0038) and sarcoma patients showed a 14% decrease (P=0.0116), whereas renal and prostate cancer patients did not show a significant decrease.

Conclusion(s): Circulating APC levels are significantly decreased in cancer patients. Differences among cancer types may be due to differential contribution of APC in tumorigenesis or by the regulation driven by cancer cells on APC levels. The reduction in circulating APC may further enhance hypercoagulability in cancer patients while reducing its cytoprotective functions, thus contributing to tumorigenesis. ISCIII-FEDER (PI17/00495, PI20/00075, FI21/00171), GVA (ACIF/2017/138) and SETH.