Colorectal carcinoma: Evaluation of systemic values of IL-1 and IL-33 in patients with and without thrombocytosis

Background/Aim. Reactive thrombocytosis, as a paraneoplastic syndrome, is often observed in cancer patients. A variety of tumor-related humoral factors and cytokines contribute to tumor-stimulated thrombopoiesis. However, the exact role of these cytokines in the pathogenesis of thrombocytosis remains unclear. The aim of this study was to analyze systemic values of cytokines and clinical-pathological characteristics in colorectal carcinoma (CRC) patients with and without thrombocytosis. Methods. In this study, 59 CRC patients were involved and divided in two groups according to the number of platelets. We recorded and analyzed the data about: age, gender, size of the cancer, localization, metastasis, vascular or lymph vessel invasion, nuclear grade, histological differentiation rate, TNM stage and concentration of cytokines (IL-1, IL-33, IL-12, IL-17 and IFN-γ) in both groups. Results. CRC patients with thrombocytosis had significantly higher nuclear grade of colorectal cancer (p=0.002); higher percentage of detectable metastatic lesions in liver (p=0.002), lung (p=0.001), peritoneal carcinomatosis (p=0.001), detectable invasion of blood (p=0.012) and lymph vessels (p=0.010), respectively. Concentrations of tumor markers AFP, CEA and CA 19-9 and serum values of IL-1 and IL-33 were significantly higher in CRC patients with thrombocytosis. IL-1/IL-12 (p=0.016), IL-1/IFN-γ (p=0.007), IL-1/IL-17 (p=0.006), IL-33/IL-12 (p=0.001), IL-33/IFN-γ (p=0.001), IL-33/IL-17 (p=0.002), and IL-33/IL-1 (p=0.006) ratios were significantly higher in CRC patients with thrombocytosis in comparison to CRC patients without thrombocytosis. Analysis of Receiver Operating Characteristic (ROC) curves showed that IL-1 (AUC=0.718; 95% Cl: 0.567-0.868); sensitivity 69,2%, specificity 62,9% and IL-33 (AUC=0.763; 95% Cl: 0.614-0.911); sensitivity 84,6%, specificity 65,7%, can serve as possible markers for paraneoplastic thrombocytosis in CRC patients. Conclusion. IL-1 and IL-33 are significantly correlated to high thrombocyte number in patients with more aggressive CRC. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175069]