Systematic literature review of IL-6 as a biomarker or treatment target in patients with gastric, bile duct, pancreatic and colorectal cancer

Abstract

Gastrointestinal cancer (GI) is a major health problem. Patients with gastric, pancreatic, colorectal, bile duct and gall bladder cancer often have advanced disease at the time of diagnosis and are generally difficult to cure, resulting in a dismal prognosis for most patients. Inflammation plays an important role in the development and growth of cancer, which has led to a growing interest in the pro-inflammatory cytokine interleukin 6 (IL-6).The aim of the present review was to evaluate the clinical use of IL-6 as a biomarker or therapeutic target in patients with GI cancer. We did a systematic review of studies (1993–2018), to assess the clinical use of IL-6 as a diagnostic, prognostic or predictive tumor biomarker or as a potential therapeutic target.This review includes 48 studies and 5316 patients. Circulating IL-6 levels appear to be an independent prognostic biomarker in patients with GI cancer, with high IL-6 levels associated with short overall survival (OS). The results for colorectal cancer were too ambiguous to give conclusive results. IL-6 seemed to be a marker for some of the clinical characteristics of GI cancer, and may have a role in the diagnostic workup in general practice. No published studies have examined the use of IL-6 as a therapeutic target in pancreatic, gastric, bile duct or colorectal cancer.In conclusion, high circulating IL-6 was associated with short OS in most studies in GI cancer patients. Whether inhibition of IL-6 would decrease GI cancer symptoms and increase quality of life is unknown.

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

“…Additionally, recent studies have indicated that high systemic IL-6 levels are linked to worse prognosis in different cancer patients (gastric, non-small lung, pancreas etc.) (33)(34)(35). However, no prior studies have examined the association IL-6mediated STAT3 activation between cancer patients with cancer cachexia, to our knowledge.…”

“…Although cachexia is generally observed in pancreatic, gastric, colorectal, lung, and head and neck cancer, recent studies have provided a compelling evidence that there is a relationship between advance metastatic breast cancer and cachexia due to a decrease in muscle mass and excessive weight loss (53)(54)(55). Recent studies have also demonstrated that a high level of IL-6 is associated with cachexia, angiogenesis, atrophy, increased catabolism of muscle protein and resistance to treatment in advance breast cancer (2,35,56). Furthermore, breast cancer patients with high levels of IL-6 compared to the heathy control groups indicate cachexia symptoms and are characterized by weight loss (33,57,58).…”

Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy

“…Furthermore, the molecular orchestra mediating SIR in colorectal cancer patients is complex. We chose circulating IL-6 as a marker since it has been proposed as one of the key mediators of SIR in mCRC as a result of tumor necrosis [26,27]. Still this is a simplification of reality, and other markers could have strengthened predictions and complemented interpretations.…”

Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer

“…PC is characterized by pronounced inflammation and disperse tumor cells in a dense desmoplastic stroma consisting of pancreatic stellate cells (PSCs), carcinoma‐associated fibroblasts, extracellular matrix (ECM), endothelial cells and immune cells. Interaction between stroma and inflammation is reported . Stroma contributes to the hypoxic and avascular microenvironment in both primary tumors and metastases .…”

“…Interaction between stroma and inflammation is reported. [8][9][10][11][12] Stroma contributes to the hypoxic and avascular microenvironment in both primary tumors and metastases. 7,13 However, stromal biology and its prognostic impact are still under discussion.…”