Abstract
BackgroundThe receptor for advanced glycation end-product (RAGE) is a multi-ligand receptor involved in inflammation. In the gene encoding RAGE (AGER), there are three well-known polymorphisms; rs2070600, rs1800624, and rs1800625, which potentially increase the risk of lung cancer. Remarkably, AGER rs2070600 polymorphism, which increases ligand-binding affinity, is a potential prognostic factor in non-small cell lung cancer, but the underlying mechanism is unclear. The neutrophil-lymphocyte ratio (NLR) reflects tumor-associated systemic inflammatory conditions; high ratios are associated with poor prognosis in multiple cancers. Additionally, some humoral factors via RAGE-signaling are associated with elevated NLR in cancer patients.ObjectivesAssociations of AGER polymorphisms with disease susceptibility, prognosis, and NLR were investigated in Japanese patients with lung adenocarcinoma.MethodsWe included 189 patients with lung adenocarcinoma, 96 of which had distant metastases, and 303 healthy controls. The correlation between AGER polymorphisms (rs2070600, rs1800624, rs1800625) and disease susceptibility and factors elevating the mortality and NLR in patients with metastases were evaluated.ResultsOnly the minor allele of rs2070600 was associated with a higher NLR (β = 0.209, p = 0.043) and a poor prognosis (Hazard ratio = 2.06, 95% Confidence interval = 1.09–3.77, p = 0.028) in patients with metastatic disease, independently of background characteristics, including EGFR mutation status. All three polymorphisms were not associated with the risk of lung adenocarcinoma.ConclusionsThe AGER rs2070600 polymorphism was independently associated with systemic inflammation and poor prognosis in patients with metastatic lung adenocarcinoma.
Highlights
Lung cancer is the leading cause of cancer deaths worldwide; the most common form of lung cancer is lung adenocarcinoma in both non-smokers and smokers [1]
Only the minor allele of rs2070600 was associated with a higher neutrophil-lymphocyte ratio (NLR) (β = 0.209, p = 0.043) and a poor prognosis (Hazard ratio = 2.06, 95% Confidence interval = 1.09–3.77, p = 0.028) in patients with metastatic disease, independently of background characteristics, including epidermal growth factor receptor (EGFR) mutation status
The AGER rs2070600 polymorphism was independently associated with systemic inflammation and poor prognosis in patients with metastatic lung adenocarcinoma
Summary
Lung cancer is the leading cause of cancer deaths worldwide; the most common form of lung cancer is lung adenocarcinoma in both non-smokers and smokers [1]. Recent work has demonstrated that tumor-associated systemic inflammatory conditions might be a prognostic factor in cancer patients [5, 6]. Previous studies have shown that post-RAGE signaling promotes the production of several growth factors and cytokines, e.g., platelet-derived growth factor (PDGF), interleukin-6 (IL6), and monocyte chemotactic protein-1 (MCP-1) [13], which might be associated with aggravating tumor-related systemic inflammation and elevated NLRs [14, 15]. AGER rs2070600 polymorphism, which increases ligand-binding affinity, is a potential prognostic factor in non-small cell lung cancer, but the underlying mechanism is unclear. The neutrophil-lymphocyte ratio (NLR) reflects tumor-associated systemic inflammatory conditions; high ratios are associated with poor prognosis in multiple cancers. Some humoral factors via RAGE-signaling are associated with elevated NLR in cancer patients
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