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Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival.

ABSTRACT: Differentially methylated regions (DMRs) within DNA isolated from whole blood can be used to estimate the proportions of circulating leukocyte subtypes. We use the term "immunomethylomics" to describe the application of these immune lineage DMRs to studying leukocyte profiles. Here, we applied this approach to peripheral blood DNA from 72 glioma patients with molecularly defined brain tumors, representing common patient groups with defined characteristic survival times and risk factors. We first estimated the proportions of leukocyte subtypes in samples using deconvolution algorithms with reference DMR libraries from isolated leukocyte populations and Illumina 450K DNA methylation data. Then, we calculated the neutrophil to lymphocyte ratio (NLR) using methylation-derived cell composition estimates (mdNLR). The NLR is considered an indicator of immunosuppressive cells in cancer patients.Elevated mdNLR scores were observed in glioma patients compared to mdNLR values of published controls. Significantly decreased survival times were associated with mdNLR???4.0 in Cox proportional hazards models adjusted for age, gender, tumor grade, and molecular subtype (HR 2.02, 95% CI, 1.11-3.69). We also identified five myeloid-related CpGs that were highly correlated with the mdNLR (adjusted R2???0.80). Each of the five myeloid CpG loci was associated with survival when adjusted for the above covariates and offer a simplified approach for utilizing fresh or archived peripheral blood samples for interrogating a very small number of methylation markers to estimate myeloid immune influences in glioma survival.The mdNLR (based on DNA methylation) is a novel candidate methylation biomarker that represents immunosuppressive myeloid cells within the blood of glioma patients with potential application in clinical trials and future epidemiologic studies of glioma risk and survival.

SUBMITTER: Wiencke JK

PROVIDER: S-EPMC5288996 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival.

Wiencke John K JK Koestler Devin C DC Salas Lucas A LA Wiemels Joseph L JL Roy Ritu P RP Hansen Helen M HM Rice Terri T McCoy Lucie S LS Bracci Paige M PM Molinaro Annette M AM Kelsey Karl T KT Wrensch Margaret R MR Christensen Brock C BC

Clinical epigenetics 20170202

<h4>Background</h4>Differentially methylated regions (DMRs) within DNA isolated from whole blood can be used to estimate the proportions of circulating leukocyte subtypes. We use the term "immunomethylomics" to describe the application of these immune lineage DMRs to studying leukocyte profiles. Here, we applied this approach to peripheral blood DNA from 72 glioma patients with molecularly defined brain tumors, representing common patient groups with defined characteristic survival times and ris ...[more]

PMID: 28184256

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Project description:IntroductionStage IIB cervical cancer (CC) is an advanced stage CC with poor prognosis. Inflammatory response plays a crucial role in the development of CC, and systemic inflammatory indexes were related to the prognosis in several cancers. The objective of the study was to determine the prognostic value of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and systemic inflammation response index (SIRI) as inflammatory indexes in patients with stage IIB CC.Materials and methodsA retrospective study was performed in 260 patients with stage IIB CC. PLR, NLR, MLR, BLR, and SIRI were obtained from routine blood tests. Prognosis information of the patients was acquired from regular clinical follow-up. Recurrence and response to therapy were determined through electronic medical records (EMRs). Correlations of the inflammatory indexes with overall survival (OS), progression-free survival (PFS), recurrence, and response to therapy were analyzed using SPSS version 26.0 software.ResultsReceiver operating characteristic (ROC) curve analyses suggested that NLR, MLR, and SIRI had better predictive value than PLR as well as BLR in the prognosis and recurrence risk. Both univariate and multivariate survival analyses showed that higher NLR and MLR were significantly associated with shorter OS as well as PFS, whereas SIRI was not an independent predictive factor of PFS. Chi-square test results revealed that increased NLR was significantly correlated with higher recurrence rate (P=0.046), and increased MLR showed significant correlation with elevated recurrence risk (P=0.002). Univariate and binary logistic regression analyses for response to therapy indicated that elevated NLR was associated with decreased complete remission (CR) rate (P=0.031), and the P value lost statistical significance while being adjusted by tumor size (P=0.108).ConclusionsFor patients with stage IIB CC, both NLR and MLR are independent prognostic factors as well as risk factors for recurrence; NLR serves as a potential marker for therapeutic response.

Dataset Information

Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival.

Publications

Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival.

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