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AGER rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma.

ABSTRACT: The 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.Associations of AGER polymorphisms with disease susceptibility, prognosis, and NLR were investigated in Japanese patients with lung adenocarcinoma.We 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.Only the minor allele of rs2070600 was associated with a higher NLR (? = 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.The AGER rs2070600 polymorphism was independently associated with systemic inflammation and poor prognosis in patients with metastatic lung adenocarcinoma.

SUBMITTER: Yamaguchi K

PROVIDER: S-EPMC5706881 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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<i>AGER</i> rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma.

Yamaguchi Kakuhiro K Iwamoto Hiroshi H Sakamoto Shinjiro S Horimasu Yasushi Y Masuda Takeshi T Miyamoto Shintaro S Nakashima Taku T Ohshimo Shinichiro S Fujitaka Kazunori K Hamada Hironobu H Hattori Noboru N

Oncotarget 20171010 55

<h4>Background</h4>The receptor for advanced glycation end-product (RAGE) is a multi-ligand receptor involved in inflammation. In the gene encoding RAGE (<i>AGER</i>), there are three well-known polymorphisms; rs2070600, rs1800624, and rs1800625, which potentially increase the risk of lung cancer. Remarkably, <i>AGER</i> 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 neu ...[more]

PMID: 29212235

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Project description:We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52-0.65, p = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53-0.70, p < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27-3.12, p < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90-2.30, p = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79-5.01, p < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.

Project description:BackgroundThe neutrophil-lymphocyte ratio (NLR) has been recognized as a useful marker of poor prognosis in non-cardiac surgery patients. But, the prognostic function of NLR in cardiovascular surgery patients still largely unknown. The aim of this study was to explore the relationship between postoperative NLR and mortality in cardiac surgery patients.MethodsClinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Postoperative day 1 (POD-1) NLR of the patients was calculated. All patients were divided into two groups according to the cut-off value of NLR, which was determined using the receiver operating characteristic (ROC) curve and Youden Index. The primary death outcomes were 30-day, 90-day and 1-year mortality. Cox proportional hazard analysis was performed to assess the associations between NLR and 1-year mortality. Logistic analysis was performed to assess the associations between NLR and other outcomes. Multivariate analyses were used to control for confounders.ResultsA total of 2,707 cardiac surgery patients were included in this study. The cut-off value of postoperative NLR was 7.28. Elevated postoperative NLR was associated with increased death outcomes including 30-day mortality [adjusted odds ratio (OR) 2.25, P=0.019], 90-day mortality (adjusted OR 2.49, P=0.001) and 1-year mortality [adjusted hazard ratio (HR) 1.58, P=0.03] of cardiac surgery in cox proportional hazard model. Elevated NLR was also associated with increased risk of continuous renal replacement therapy (CRRT) rate (adjusted OR 3.01, P=0.004), prolonged ICU stays (adjusted OR 2.55, P<0.001), prolonged hospital stays (adjusted OR 3.32, P<0.001) and duration of ventilatory support (adjusted OR 4.16, P<0.001) after adjusting confounders.ConclusionsElevated postoperative NLR was significantly associated with increased short-term and long-term mortality, CRRT rate, longer ICU and hospital stay, prolonged ventilation in patients undergoing cardiac surgery. NLR is promising to be a readily available and independent prognostic biomarker for patients with cardiac surgery.

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AGER rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma.

Publications

<i>AGER</i> rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma.

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