Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis

Abstract

BackgroundPrevious evidence indicated that Helicobacter pylori-induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to H. pylori infection and GC and relate these to global GC risk.MethodsWe performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in H. pylori-infected cases vs. non-infected controls and gastric cancer cases vs. non-gastric cancer controls, with sub-analyses performed to identify global regional differences in cytokine induction and their correlation with GC incidence.ResultsOnly levels of systemic IL-6 (standardized mean difference [SMD]:0.95, 95%CI [0.45;1.45]) and TNF-α (SMD:0.88, 95%CI [0.46; 1.29]) were significantly increased upon H. pylori infection. Sub-analysis showed that of IL-6 levels were increased upon H. pylori infection in East Asian, Middle Eastern and Southeast Asian cohorts, but not in North America, Europe, Russia and Africa. Serum levels of IL-6, IL-7, IL-10, IL-12, and TNF-α were significantly raised in GC. Exploration of the relationship between serum cytokines changes upon H. pylori infection and regional differences in risk of GC development indicated that the SMD of IL-6 serum levels presents a significant correlation with the relative incidence of GC (r=0.81, p=0.00014).ConclusionThis study shows that H. pylori infection and GC are associated with increased IL-6 and TNF-α levels. Particularly, IL-6 shows region-specific increases that correlate with GC incidence, making it a key contender for the cause of this disease.

IL-6 facilitates cross-talk between epithelial cells and tumor- associated macrophages in Helicobacter pylori-linked gastric carcinogenesis

“…The mechanism behind H. pylori -associated inflammation and GC development remains incompletely understood, and identifying factors that could contribute to these processes remains important. A previous meta-analysis identified IL-6 as a potential key factor in this process [11] , making it a subject for further investigation. We aimed to explore the role of IL-6 in H. pylori -associated gastric cancer and show that macrophages and epithelial cells demonstrate both autocrine and paracrine IL-6 induction, which is enhanced by H. pylori .…”

“…Multiple lines of evidence indicate that the pro-inflammatory cytokine interleukin-6 (IL-6) is a crucial factor in gastric carcinogenesis [6] , [7] , [8] , [9] , [10] . Previous studies showed a substantial and relevant association between the systemic IL-6 levels induced by H. pylori -infection and the relative incidence of GC [11] . IL-6 serum levels are increased in GC patients, and are associated with disease progression and worse prognosis [ 9 , 12 ].…”

Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance

“…In immune cells at the site of infection, the expression of proinflammatory cytokines and the chemokine CCL5 increases, key in the development of chronic gastric inflammation and the onset of GC ( 23 ). In a meta-analysis study of the literature, a significant increase in circulating levels of IL-6 and TNF-a was found during infection with the bacteria, when it was also associated with GC, increased serum levels of IL-6 IL-7, IL-10, IL-12 and TNF-a were found ( 24 ). Another study demonstrated that the presence of the bacteria favors the activation of nuclear factor kappa B (NF-kB) in gastric epithelial cells, generating the release of inflammatory mediators such as interleukin-8 (IL-8) ( 25 ).…”

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer

“…Gastric cancer, also known as stomach cancer, is a relatively common malignancy, being the third most common cause of cancer-related deaths worldwide (Lu et al 2022 ; Ma et al 2022 ). With a relative five-year survival rate below 30% in its advanced stage, it has a poor prognosis and represents a substantial socio-medical burden that remains to be addressed (Yu et al 2023 ). Research on the disease has linked numerous non-coding RNAs to its onset and malignant spread.…”