Dataset Information

DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio: An Epigenetic Tool to Explore Cancer Inflammation and Outcomes.

ABSTRACT: Background: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a cytologic marker of both inflammation and poor outcomes in patients with cancer. DNA methylation is a key element of the epigenetic program defining different leukocyte subtypes and may provide an alternative to cytology in assessing leukocyte profiles. Our aim was to create a bioinformatic tool to estimate NLR using DNA methylation, and to assess its diagnostic and prognostic performance in human populations.Methods: We developed a DNA methylation-derived NLR (mdNLR) index based on normal isolated leukocyte methylation libraries and established cell-mixture deconvolution algorithms. The method was applied to cancer case-control studies of the bladder, head and neck, ovary, and breast, as well as publicly available data on cancer-free subjects.Results: Across cancer studies, mdNLR scores were either elevated in cases relative to controls, or associated with increased hazard of death. High mdNLR values (>5) were strong indicators of poor survival. In addition, mdNLR scores were elevated in males, in nonHispanic white versus Hispanic ethnicity, and increased with age. We also observed a significant interaction between cigarette smoking history and mdNLR on cancer survival.Conclusions: These results mean that our current understanding of mature leukocyte methylomes is sufficient to allow researchers and clinicians to apply epigenetically based analyses of NLR in clinical and epidemiologic studies of cancer risk and survival.Impact: As cytologic measurements of NLR are not always possible (i.e., archival blood), mdNLR, which is computed from DNA methylation signatures alone, has the potential to expand the scope of epigenome-wide association studies. Cancer Epidemiol Biomarkers Prev; 26(3); 328-38. ©2016 AACR.

SUBMITTER: Koestler DC

PROVIDER: S-EPMC5336518 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio: An Epigenetic Tool to Explore Cancer Inflammation and Outcomes.

Koestler Devin C DC Usset Joseph J Christensen Brock C BC Marsit Carmen J CJ Karagas Margaret R MR Kelsey Karl T KT Wiencke John K JK

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20161213 3

<b>Background:</b> The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a cytologic marker of both inflammation and poor outcomes in patients with cancer. DNA methylation is a key element of the epigenetic program defining different leukocyte subtypes and may provide an alternative to cytology in assessing leukocyte profiles. Our aim was to create a bioinformatic tool to estimate NLR using DNA methylation, and to assess its diagnostic and prognostic performance in human populations.<b>Me ...[more]

PMID: 27965295

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Project description:Introduction and objectives In patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease. Materials and methods The study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR. Results A total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91–10.46) and 4.00 (2.33–6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay (p < 0.001), death (p < 0.001), and invasive ventilation (p < 0.001) while that of dNLR with ICU stay (p = 0.002), death (p < 0.001), and invasive ventilation (p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT). Conclusion Both markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients.

Project description:BackgroundThe highly heterogeneous characteristics of GC may limit the accuracy of a single biomarker for screening populations benefiting from immunotherapy. However, the combination of multiple indicators can provide more directed information for the detection of potential immune benefit subgroups. At present, there are no recognized complex indexes to identify advanced GC (AGC) in patients who likely benefited from immunotherapy. The objective of this research is to explore whether the composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and platelet-lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy.MethodsFrom December 2014 to May 2021, a total 238 AGC patients at a single Center were included in this retrospective cohort research study. The cutoff value of dNLR was obtained by the ROC curves to predict the disease progression rate at the 8th month and the cutoff value of PLR was estimated by the median value. The cutoff values of dNLR and PLR were 1.95 and 163.63, respectively. The high levels of dNLR (≥1.95) and PLR (≥163.63) were considered to be risk factors. Based on these two risk factors, patients were categorized into 3 groups: the risk factor number for the "good" group was 0, that for the "intermediate" group was 1, and that for the "poor" group was 2. The subjects were divided into two groups: dNLR/PLR-good and dNLR/PLR-intermediate/poor.ResultsOf the 238 patients, the median overall survival (mOS) and progression-free survival (mPFS) were 12.5 and 4.7 months, respectively. Multivariate analysis revealed that the good dNLR/PLR group was independently associated with better prognosis. The intermediate/poor dNLR/PLR group was independently correlated with an over 1.4 times greater risk of disease progression (4.1 months vs. 5.5 months; p = 0.016) and an over 1.54 times greater risk of death (11.1 months vs. 26.3 months; p = 0.033) than the good dNLR/PLR group. However, no clear differences in the disease control rate (DCR) and overall response rate (ORR) were observed between the intermediate/poor dNLR/PLR group and the good dNLR/PLR group (51.5% vs. 56.3%, 26.3% vs. 29.6%; p = 0.494, p = 0.609).ConclusionOur study firstly verifies that the composite biomarker of dNLR and PLR is an independent prognostic factor affecting survival of advanced AGC patients receiving immunotherapy. It may be difficult for patients with the intermediate/poor dNLR/PLR group to benefit from immunotherapy.

Project description:Acute Limb Ischemia (ALI) of the lower limb is defined as a sudden drop in arterial limb perfusion, which is a medical emergency requiring prompt intervention with high amputation and mortality rates in the absence of revascularization. This observational, analytical, and retrospective cohort study with longitudinal follow-up aimed to confirm the relevance of the preoperative inflammatory biomarkers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the 30-day poor prognosis of patients with Rutherford classification (RC) grades II and III ALI. The ROC analysis found a strong association of an NLR > 4.33 with all studied outcomes, while a PLR > 143.34 was associated with all studied outcomes, except the composite endpoint in all RC stages. Depending on the optimal cut-off value, the ROC analysis found a higher incidence of all adverse outcomes in all high NLR (>4.33) and high PLR (>143.34) groups. A multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of amputation (OR:11.09; 95% CI: 5.48-22.42; p < 0.0001; and OR:8.97; 95% CI: 4.44-18.16; p < 0.0001), mortality (OR:22.24; 95% CI: 9.61-51.47; p < 0.0001; and OR:8.32; 95% CI: 3.90-17.73; p < 0.0001), and composite endpoint (OR:21.93; 95% CI: 7.91-60.79; p < 0.0001; and OR:9.98; 95% CI: 3.89-25.55; p < 0.0001), respectively. Furthermore, for all hospitalized patients, the RC grade III (OR:7.33; 95% CI: 3.73-14.26; p < 0.0001) was an independent predictor of amputation (OR:7.33; 95% CI: 3.73-14.26; p < 0.0001), mortality (OR:8.40; 95% CI: 4.08-17.31; p < 0.0001), and composite endpoint (OR: 10.70; 95% CI: 4.48-25.56; p < 0.0001), respectively. The NLR and PLR are excellent predictors of risks associated with ALI for primary and secondary prevention. Our study showed that increased pre-operative values for NLR and PLR are indicators of a poor outcome in patients with RC grades II and III ALI.

Dataset Information

DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio: An Epigenetic Tool to Explore Cancer Inflammation and Outcomes.

Publications

DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio: An Epigenetic Tool to Explore Cancer Inflammation and Outcomes.

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