Sex-dependent association of preoperative hematologic markers with glioma grade and progression
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Neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio, the systemic immune-inflammation index (SII), and red blood cell distribution width (RDW), have been recognized as promising predictors for histological grade and prognosis in multiple cancer types. However, few investigations illustrated the impacts of sex on the clinical utility of hematologic markers. Patients with primary gliomas were retrospectively reviewed. The association between grade and inflammatory markers by sex were investigated by univariate and multivariate analysis. The discrimination ability of logistic regression model was evaluated by the area under the receiver-operating characteristic curve (AUC) for high-grade glioma (HGG). Kaplan–Meier progressionfree survival (PFS) curves were plotted to assess the prognostic value of RDW. In subgroup analysis, distinctively elevated NLR and SII levels were exclusively present in male HGGs group (p = 0.001); whereas RDW notably increased in female HGGs group (p = 0.001). On multivariate analysis, increased odds ratio of HGGs was exclusively observed for female patients with elevated RDW (odds ratio = 1.589). Moreover, regression model developed by RDW exhibited an excellent discriminative ability for the prediction of HGGs in female patients (AUC = 0.817). Median progression time with RDW < 13.2 versus RDW ≥ 13.2 was 62.5 versus 33.0 months (log rank p = 0.017). Older females (≥ 45 years) with increased RDW levels portended worse survival (HR 3.693, 95% CI 1.747–8.325, p = 0.001). Meanwhile, the significant association of RDW levels with PFS in male subgroup was not observed (p > 0.05). In conclusion, superior to NLR and SII, RDW would be sex-specific predictor for tumor grade and progression for HGG female patients.
KeywordsGlioma Sex Systemic immune-inflammation index Neutrophil-to-lymphocyte ratio Red blood cell distribution width
Body mass index
Red blood cell distribution width
Mean corpuscular volume
White blood cell
Mean platelet volume
Hepatitis B virus surface antigen
Red blood cell
Systemic immune-inflammation index
High-sensitivity C-reactive protein
Erythrocyte sedimentation rate
The area under the receiver-operating characteristic curve
This work was sponsored by Medical Elite Cultivation Program of Fujian Provincial Commission of Health and Family Planning, P.R.C (No. 2016ZQN44) and Startup Fund for Scientific Research, Fujian Medical University (No. 2016Y91010119), and Educational and Scientific Research Program of Fujian Provincial Department of Education (No. JAT170240).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
For this retrospective study formal consent is not required.
- 3.Cancer tIAfRo (2016) WHO classification of tumours of the central nervous system, revised, 4th edn. WHO Press, World Health Organization, GenevaGoogle Scholar
- 4.Trinchieri G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Ann Rev Immunol 30:677–706. https://doi.org/10.1146/annurev-immunol-020711-075008 CrossRefGoogle Scholar
- 6.Kawahara T, Fukui S, Sakamaki K, Ito Y, Ito H, Kobayashi N, Izumi K, Yokomizo Y, Miyoshi Y, Makiyama K, Nakaigawa N, Yamanaka T, Yao M, Miyamoto H, Uemura H (2015) Neutrophil-to-lymphocyte ratio predicts prostatic carcinoma in men undergoing needle biopsy. Oncotarget 6(31):32169–32176. https://doi.org/10.18632/oncotarget.5081 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Bambury RM, Teo MY, Power DG, Yusuf A, Murray S, Battley JE, Drake C, O’Dea P, Bermingham N, Keohane C, Grossman SA, Moylan EJ, O’Reilly S (2013) The association of pre-treatment neutrophil to lymphocyte ratio with overall survival in patients with glioblastoma multiforme. J Neuro Oncol 114(1):149–154. https://doi.org/10.1007/s11060-013-1164-9 CrossRefGoogle Scholar
- 9.Wang L, Wang C, Wang J, Huang X, Cheng Y (2017) A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. https://doi.org/10.1007/s00432-017-2451-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC (2009) Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 133(4):628–632. https://doi.org/10.1043/1543-2165-133.4.628 CrossRefGoogle Scholar
- 14.Fu Y, Mao Y, Chen S, Yang A, Zhang Q (2016) A novel inflammation- and nutrition-based prognostic system for patients with laryngeal squamous cell carcinoma: combination of red blood cell distribution width and body mass index (COR-BMI). PLoS ONE 11(9):e0163282. https://doi.org/10.1371/journal.pone.0163282 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Hirahara N, Matsubara T, Kawahara D, Mizota Y, Ishibashi S, Tajima Y (2016) Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma. Int J Clin Oncol 21(5):909–919. https://doi.org/10.1007/s10147-016-0986-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–ii56. https://doi.org/10.1093/neuonc/not151 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Wang BL, Tian L, Gao XH, Ma XL, Wu J, Zhang CY, Zhou Y, Guo W, Yang XR (2016) Dynamic change of the systemic immune inflammation index predicts the prognosis of patients with hepatocellular carcinoma after curative resection. Clin Chem Lab Med 54(12):1963–1969. https://doi.org/10.1515/cclm-2015-1191 CrossRefPubMedGoogle Scholar
- 24.Zhang JW, Huang L, Xu AM (2017) Preoperative monocyte-lymphocyte and neutrophil-lymphocyte but not platelet-lymphocyte ratios are predictive of clinical outcomes in resected patients with non-metastatic Siewert type II/III adenocarcinoma of esophagogastric junction: a prospective cohort study (the AMONP corhort). Oncotarget. https://doi.org/10.18632/oncotarget.15497 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Xu WS, Qiu XM, Ou QS, Liu C, Lin JP, Chen HJ, Lin S, Wang WH, Lin SR, Chen J (2015) Red blood cell distribution width levels correlate with liver fibrosis and inflammation: a noninvasive serum marker panel to predict the severity of fibrosis and inflammation in patients with hepatitis B. Medicine (Baltimore) 94(10):e612. https://doi.org/10.1097/md.0000000000000612 CrossRefGoogle Scholar
- 31.Friedman JS, Lopez MF, Fleming MD, Rivera A, Martin FM, Welsh ML, Boyd A, Doctrow SR, Burakoff SJ (2004) SOD2-deficiency anemia: protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness. Blood 104(8):2565–2573. https://doi.org/10.1182/blood-2003-11-3858 CrossRefPubMedGoogle Scholar
- 35.Gwak MS, Choi SJ, Kim JA, Ko JS, Kim TH, Lee SM, Park JA, Kim MH (2007) Effects of gender on white blood cell populations and neutrophil-lymphocyte ratio following gastrectomy in patients with stomach cancer. J Korean Med Sci 22(Suppl):S104–S108. https://doi.org/10.3346/jkms.2007.22.S.S104 CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Diaz-Castro J, Pulido-Moran M, Moreno-Fernandez J, Kajarabille N, de Paco C, Garrido-Sanchez M, Prados S, Ochoa J (2016) Gender specific differences in oxidative stress and inflammatory signaling in healthy term neonates and their mothers. Pediatr Res 80(4):595–601. https://doi.org/10.1038/pr.2016.112 CrossRefPubMedGoogle Scholar
- 38.Pilling L, Atkins J, Duff M, Beaumont R, Jones S, Tyrrell J, Kuo C, Ruth K, Tuke M, Yaghootkar H, Wood A, Murray A, Weedon M, Harries L, Kuchel G, Ferrucci L, Frayling T, Melzer D (2017) Red blood cell distribution width: genetic evidence for aging pathways in 116,666 volunteers. PLoS ONE 12(9):e0185083. https://doi.org/10.1371/journal.pone.0185083 CrossRefPubMedPubMedCentralGoogle Scholar
- 42.von Haehling S, Gremmler U, Krumm M, Mibach F, Schön N, Taggeselle J, Dahm J, Angermann C (2017) Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: the PrEP Registry. Clin Res Cardiol 106(6):436–443. https://doi.org/10.1007/s00392-1073-y CrossRefGoogle Scholar