Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study

Background: 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. Methods: We 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-1 beta IL-6, TNF-alpha, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-gamma, and TGF-beta in plasma were measured using enzyme-linked immunosorbent assay. Results: Levels of IL-1 beta, IL-6, IFN-gamma, 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-alpha levels were observed between gastric cancer and controls. IFN-gamma and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1 beta and IL-6 were higher and TGF-beta lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-gamma and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1 beta 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-1 beta and IFN-gamma showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively). Conclusions: Increased levels of IL-6, IFN-gamma, 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-1 beta, IL-6, MCP-1, and TGF-beta differentiate intestinal from diffuse GC. IFN-gamma and IL-10 might be useful for diagnosis of early stage GC, and IL-1 beta, IL-8, and MCP-1 for late stages of the disease.