The relationship between IL-6 and thrombocytosis accompanying gastrointestinal tumours

Abstract

Introduction Several reports have stated that thrombocytosis is associated with worse survival and higher rate of metastasis in solid tumours. A study in ovarian tumours implicated IL-6 produced by tumour cells as a key mechanistic factor. Aim To evaluate the relevance of this paraneoplastic pathway in gastrointestinal cancer. Material and methods After excluding thromboembolic and inflammatory disorders, 161 patients were enrolled who had been operated due to various gastrointestinal cancer at the 1 st Department of Surgery at the Semmelweis University between 2015 and 2017. Platelet counts and serum IL-6 levels were determined from preoperative blood samples. Thrombocytosis was defined as the upper limit of normal platelet count, e.g. 400 × 10 3 /µl. Results A weak but significantly positive correlation was found between elevated platelet counts and serum IL-6 (correlation coefficient: R = 0.214, p = 0.006), which became more pronounced in colon and oesophageal cancer if evaluated in the different tumour types ( R = 0.292 and R = 0.419, respectively). However, using a multivariant linear regression model ( R 2 = 0.47) corrected with haemoglobin, white blood cell count, and advanced disease stage, the analysis showed no significant correlation between serum IL-6 and platelet counts. Conclusions In gastrointestinal cancer our study did not support the paracrine-mediated paraneoplastic pathway described in ovarian tumors. Thrombocytosis showed significant correlation with white blood cells instead of serum IL-6, which implies that the inflammatory process may influence both parameters. Further studies are needed on larger patient cohorts.

Thrombocytosis in 158 cats (2011–2018)

“…In people, gastrointestinal carcinomas are commonly associated with thrombocytosis, and in certain tumor types, such as colorectal carcinoma, thrombocytosis is a negative prognostic indicator. 23 – 25 Carcinoma was an uncommon diagnosis in this study, but gastrointestinal lymphoma as well as gastrointestinal inflammatory diseases were more frequently diagnosed in cats with thrombocytosis when compared with the control group. Gastrointestinal carcinoma tumor cells have been shown to produce IL-6, which, in turn, increases thrombopoiesis.…”

“…Gastrointestinal carcinoma tumor cells have been shown to produce IL-6, which, in turn, increases thrombopoiesis. 25 It is not known if tumor cells in feline lymphoma directly produce IL-6 as a paraneoplastic mechanism, but IL-6 may be produced as part of the inflammatory milieu of the tumor’s chronic clinical progression, especially in virus-associated feline lymphoma. 13 , 26 – 28 Feline small intestinal lymphoma has a T-cell predominant phenotype and is associated with chronic inflammatory and neoplastic changes to the gastrointestinal tract.…”

Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?

“…In an earlier study [ 20 ], we have reported that a personalized, relative platelet measure can predict disease outcome significantly better than “traditional” thrombocytosis, which further strengthened that the definition of thrombocytosis needs to be revised. The biochemical detection of paraneoplastic thrombocytosis in CRC is a novel research area [ 36 ]. In the current study, we observed higher interleukin-6 and thrombopoietin levels of CRC patients, compared to those of control subjects, supporting the presence of paraneoplastic thrombocytosis, which was further strengthened by the result of correlation and survival analysis, in line with earlier findings [ 1 , 2 , 31 , 32 , 33 , 36 , 37 , 38 ].…”

“…The biochemical detection of paraneoplastic thrombocytosis in CRC is a novel research area [ 36 ]. In the current study, we observed higher interleukin-6 and thrombopoietin levels of CRC patients, compared to those of control subjects, supporting the presence of paraneoplastic thrombocytosis, which was further strengthened by the result of correlation and survival analysis, in line with earlier findings [ 1 , 2 , 31 , 32 , 33 , 36 , 37 , 38 ].…”

Exploitation of platelets for antitumor drug delivery and modulation of the tumor immune microenvironment

“…Several molecular mechanisms have been suggested to underlie the progression of cancer-associated thrombocytosis, which involves various tumor-associated cytokines and humoral factors directly or indirectly affecting megakaryopoiesis and thrombopoiesis during cancer development [19]. These factors notably include granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), and interleukin-1 (IL-1) [20]. Primary tumors secrete G-CSF and GM-CSF, which stimulate megakaryopoiesis in an endocrine manner and induce thrombopoiesis in people with cancer.…”