Diagnostic value of preoperative inflammatory markers in patients with glioma: a multicenter cohort study

Abstract

OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential d...

Prognostic Significance of Preoperative Systemic Cellular Inflammatory Markers in Gliomas: A Systematic Review and Meta‐Analysis

“…has reported that the prognostic significance of PLR is far less than that of NLR. The level of PLR activation occurs prior to surgery in many intracranial neoplasms, PLR may not have the ability to differentiate glioma from meningioma or acoustic neuroma . Although relatively high levels of PLR were found in patients with glioma, the underlying mechanism for the elevation still needs further investigation.…”

“…Only two studies were included. It is reported that LMR is not superior to the NLR for predicting the long‐term survival of patients with cancer, whereas it has significant diagnostic value for GBM compared with healthy controls …”

“…Complex interactions between tumor cells and inflammatory cytokines regulate tumor growth and inflammatory progression. Systemic cellular inflammatory markers can be a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis . Moreover, the pre‐operative inflammatory response is correlated with glioma grading, which can be quantified as scores for predicting glioma survival after different therapeutic methods are used .…”

“…5 Systemic cellular inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR) or lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI), may be potential prognostic factors for multiple solid tumors, including lung cancer, prostate cancer, gastric cancer, and metastatic melanoma. [6][7][8] However, the role of those peripheral blood inflammatory indicators in gliomas remains unclear and controversial. In a clinical study with 166 patients with GBM, both NLR and PLR are independent prognostic factors for OS, and a low NLR contributes to a better prognosis.…”

“…Numerous studies have indicated that systemic inflammatory responses can dramatically influence tumor growth, progression, and response to treatment . Systemic cellular inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR) or lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI), may be potential prognostic factors for multiple solid tumors, including lung cancer, prostate cancer, gastric cancer, and metastatic melanoma . However, the role of those peripheral blood inflammatory indicators in gliomas remains unclear and controversial.…”