Thromboinflammation in gastric cancer: association with body composition, tumor biology, staging and prognosis

• Grant number: 24/18717-3
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernanda Loureiro de Andrade Orsi
• Grantee: Fernanda Loureiro de Andrade Orsi
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated researchers: Erich Vinicius de Paula ; José Barreto Campello Carvalheira ; Maria Carolina Santos Mendes

Abstract

In Brazil, gastric cancer is the fifth most common cancer, with approximately 21,000 new cases annually and 13,850 deaths in 2020. Risk factors include H. pylori infection, an inadequate diet, smoking, and obesity. In addition to age, histological type, and staging, nutritional and metabolic status are critical in determining the prognosis of gastric cancer. Regarding nutritional status, sarcopenia, which affects 57% of patients, and malnutrition, which is diagnosed in about 60% of cases, are associated with postoperative complications, chemotherapy toxicity, and adverse outcomes.Among metabolic processes, cancer can lead to thromboinflammation, a state of combined activation of inflammatory and hemostatic mechanisms, with a high thrombotic risk. Tumor cells activate platelets and coagulation pathways by secreting procoagulant factors and releasing inflammatory cytokines, and proangiogenic factors. They also release extracellular vesicles that exacerbate coagulation, angiogenesis, and thrombotic risk. In gastric cancer, the incidence of thrombosis is very high,estimated at up to 11% per year. Beyond the prothrombotic state, thromboinflammation can promote tumor growth, angiogenesis, and metastasis, thereby influencing tumor aggressiveness and treatment response. In gastric cancer, mortality is twice as high in patients with thrombosis, which may be explained by the reciprocal activation of thromboinflammatory mechanisms and tumor cell growth. While anticoagulant therapy is effective in treating thrombosis, it does not improve patient survival.Targeted therapies against key elements involved in the thromboinflammatory process may play a role as adjuvant therapy in gastric cancer. In cardiovascular diseases, where thromboinflammation also impacts thrombotic risk and prognosis, the use of colchicine and anti-IL-1 antibodies has shown positive results. In this context, this study aims to analyze the relashionship between thromboinflammatory mechanisms and body composition, disease stage, and tumor genomic profile in newly diagnosed patients with gastric cancer. In addition, the association between the thromboinflammatory profile at diagnosis and the occurrence of thrombotic events, disease-free survival, and overall survival will be investigated.To this end, a prospective cohort of gastric cancer patients treated at the University of Campinas Clinical Hospital will be evaluated for several parameters associated with the interaction between inflammation and hemostasis (thrombin generation, platelet activity, extracellular vesicle release, and neutrophil extracellular trap formation). In a cross-sectional analysis, the association of these parameters with body composition and radiographic density (assessed by computed tomography) of muscle and adipose tissues will be investigated, as well as with tumor genomics and disease stage at diagnosis. In a prospective analysis, the impact of thromboinflammatory parameters on the occurrence of thrombosis, disease-free survival, and overall survival will be evaluated. We aim to improve the understanding of changes in the thromboinflammatory profile and their impact on the prognosis of gastric cancer patients, with the goal of developing tools to aid in predicting clinical outcomes and identifying new therapeutic targets. (AU)