High sensitivity multiplex cytokine panel used to identify unique signatures in serum associated with gallbladder cancer.

Abstract

Abstract Gallstones (GS) and chronic inflammation are two of the strongest risk factors associated with gallbladder cancer (GBC). Since these conditions are frequently asymptomatic, GBC detection often occurs incidentally and when the cancer has reached a progressive stage. Gaining a better understanding of the mechanisms involved in the development and progression of GBC could help identify the subpopulation of gallstone patients that will go on to develop GBC. Therefore, we sought to measure 16 key inflammatory markers in serum samples with a high sensitivity bead-based multiplex cytokine assay of population-based controls (PBC), patients with gallstone(s) (GS), and patients with gallbladder cancer (GBC), from Shanghai, China. Wilcoxon’s rank sum test was used to compare median concentrations. We found 11 markers (IL-1β, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p70), IL-13, IL-17A, IL-21, and IL-23) that were significantly (p value <0.01) elevated in GS compared to PBC; fold changes ranged from 1.3 to 1.7. We found 6 markers (MIP-1α, MIP-1β, IL-6, IL-7, IL-8, and IL-10) that were significantly elevated in GBC compared to GS; fold changes ranged from 1.2 to 3.6. Moreover, only 3 markers (IL-6, IL-7, and IL-10) were elevated in both comparison groups. The unique set of markers highlighted between the two comparison groups suggests that there is a transitional stage in the progression of disease leading up to GBC. Future studies are needed to further evaluate the common pathway or mechanism associated with these cytokine signatures. Futhermore, such studies should be replicated in bile to assess the local inflammatory response that develops in the gallbladder.