A meta-analyses on the role of IL-6 associated JAK/STAT3 signaling pathway modulation in the inflammatory bowel disease complicated colonic cancer development

Abstract

The signalling pathway of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) is suggested to be involved in various pathophysiological processes, including immune function, cell growth, differentiation, hematopoiesis and more importantly oncogenesis of distinct tumoral conditions. Interleukin (IL) 6 is a proinflammatory cytokine produced by antigen-presenting cells and non-hematopoietic cells in response to external stimuli and considered to be a key player in the development of the microenvironment of malignancy by promoting tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue. Recent studies suggest that aberrant interleukin IL6/JAK/STAT3 signaling pathway exists in both IBD and inflammation-related gastrointestinal cancers. In the present meta-analysis we aimed to analyze the relationship between IL-6/JAK/STAT3 and IBD associated colorectal carcinogenesis and the effect of the inhibition of this system on disease follow-up and management.In light of the small number of studies able to be included in the meta-analysis evidence strongly proposed that JAK/STAT3 signaling, especially via the IL-6/STAT3 axis is involved in the transition of inflammatory lesions to tumoral diseases and leading to ulcerative colitis associated colorectal cancer. For this reason, based on the evidence presented in this meta-analysis it is reasonable to suggest that targeting components of the IL-6/JAK/STAT3 signalling pathway can inhibit tumour cell growth and relieve immunosuppression in the UC associated colonic tumoral microenvironment.