Abstract
BackgroundGastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer.MethodsWe included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor–node–metastasis staging system of the International Union Against Cancer. Concentrations of IL-1β, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-β in plasma were measured using enzyme-linked immunosorbent assay.ResultsLevels of IL-1β, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1β and IL-6 were higher and TGF-β lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1β and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively).ConclusionsIncreased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1β, IL-6, MCP-1, and TGF-β differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1β, IL-8, and MCP-1 for late stages of the disease.
Highlights
Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide
In contrast to the results obtained for the whole group of Gastric cancer (GC) patients, we found that IL-1β and IL-6 levels were significantly higher in the intestinal GC (IGC) group but not in the diffuse GC (DGC) group, and that levels of macrophage chemotactic protein (MCP)-1 were significantly lower in the DGC group but not in the IGC group
The analyses showed no increase in risk associated with MCP-1, IL-8, and TNFα, whereas there was a trend to an association of diminished transforming growth factor (TGF)-β with a decreased risk of GC
Summary
Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer. Gastric cancer (GC) remains a major health problem worldwide, representing the third most common cause of death from all cancers [1]. The infection of the gastric mucosa by Helicobacter pylori represents the major risk factor in over 65% of all distal GC, and recent evidence suggests that it might play a role in proximal GC [2, 3]. The differences in the gastric inflammatory response between hosts may partially explain the different outcomes observed in H. pylori-infected patients [5]. Understanding the natural history of the infection may help to identify potential biomarkers for the early diagnosis of GC to allow timely treatment to reduce mortality
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