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

Noomi Vainer, Christian Dehlendorff, Julia S Johansen, Noomi Vainer, Christian Dehlendorff, Julia S Johansen

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.

Keywords: biomarker; gastrointestinal cancer; interleukin-6; therapeutic target.

Conflict of interest statement

CONFLICTS OF INTEREST None.

Figures

Figure 1. Pubmed search
Figure 1. Pubmed search
The review was based on six different searches using the search criteria shown in the Figure. The search criteria were combined as shown searching PubMed. Search 1 resulted in 963 articles, which were sorted by assessing the relevance of the abstract followed by a systematic reading of all non-excluded articles. Search 2 resulted in 48 articles, also sorted by assessing the relevance of the abstract followed by a systematic reading of all non-excluded articles. Search 3–6 resulted in a great number of articles. Two of the most recent articles were chosen as supporting articles. In the case of doubt of the relevance of a given article, the article was read thoroughly before deciding its relevance.
Figure 2. The meta-analysis was performed on…
Figure 2. The meta-analysis was performed on selected studies concerning colorectal cancer and pancreatic cancer
op = operated patient cohort, n.op = non-operated patient cohort.

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