Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li, Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li

Abstract

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan-Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma.

Keywords: CRP/Alb ratio; Ewing sarcoma; inflammatory biomarkers; prognosis; survival.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Comparison of the areas under the ROC curves among the inflammation-based prognostic indicators. Abbreviations: CRP/Alb ratio, C-reactive protein to albumin ratio; GPS, Glasgow Prognostic Score; NLR, neutrophil–lymphocyte ratio; PLR, platelet–lymphocyte ratio; LMR, lymphocyte–monocyte ratio; NPS, neutrophil–platelet score.
Figure 2
Figure 2
Kaplan–Meier survival curves for overall survival according to (A) C-reactive protein to albumin ratio, (B) the Glasgow prognostic score, (C) neutrophil to lymphocyte ratio, (D) platelet to lymphocyte ratio, (E) lymphocyte to monocyte ratio, and (F) neutrophil–platelet score. Abbreviations: CRP/Alb ratio, C-reactive protein to albumin ratio; GPS, Glasgow Prognostic Score; NLR, neutrophil–lymphocyte ratio; PLR, platelet–lymphocyte ratio; LMR, lymphocyte–monocyte ratio; NPS, neutrophil–platelet score.

References

    1. Gaspar N, Hawkins DS, Dirksen U, et al. Ewing sarcoma: current management and future approaches through collaboration. J Clin Oncol. 2015;33(27):3036–3046.
    1. Jiang Y, Ludwig J, Janku F. Targeted therapies for advanced Ewing sarcoma family of tumors. Cancer Treat Rev. 2015;41(5):391–400.
    1. Li YJ, Dai YL, Cheng YS, Zhang WB, Tu CQ. Positron emission tomography (18)F-fluorodeoxyglucose uptake and prognosis in patients with bone and soft tissue sarcoma: a meta-analysis. Eur J Surg Oncol. 2016;42(8):1103–1114.
    1. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–444.
    1. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493–e503.
    1. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res. 2009;15(2):425–430.
    1. Gu X, Sun S, Gao XS, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients. Sci Rep. 2016;6:23893.
    1. Koh CH, Bhoo-Pathy N, Ng KL, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer. 2015;113(1):150–158.
    1. Li Y, Wang C, Xu M, et al. Preoperative NLR for predicting survival rate after radical resection combined with adjuvant immunotherapy with CIK and postoperative chemotherapy in gastric cancer. J Cancer Res Clin Oncol. 2017;143(5):861–871.
    1. Altan M, Haberal HB, Akdoğan B, Özen H. A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterec-tomy due to upper urinary tract urothelial carcinoma. Int J Clin Oncol. 2017 Jun 9; Epub.
    1. Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Shibuya N, Kubota K. Clinical significance of the C-reactive protein to albumin ratio for survival after surgery for colorectal cancer. Ann Surg Oncol. 2016;23(3):900–907.
    1. Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3(1):32–35.
    1. Liu Z, Jin K, Guo M, et al. Prognostic value of the CRP/Alb ratio, a novel inflammation-based score in pancreatic cancer. Ann Surg Oncol. 2017;24(2):561–568.
    1. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–7259.
    1. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–545.
    1. Heikkilä K, Ebrahim S, Lawlor DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health. 2007;61(9):824–833.
    1. Jab łońska E, Kiluk M, Markiewicz W, Piotrowski L, Grabowska Z, Jabłoński J. TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients. Arch Immunol Ther Exp (Warsz) 2001;49(1):63–69.
    1. McCourt M, Wang JH, Sookhai S, Redmond HP. Activated human neutrophils release hepatocyte growth factor/scatter factor. Eur J Surg Oncol. 2001;27(4):396–403.
    1. McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev. 2013;39(5):534–540.
    1. Shamamian P, Schwartz JD, Pocock BJ, et al. Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol. 2001;189(2):197–206.
    1. Kantola T, Klintrup K, Väyrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer. 2012;107(10):1729–1736.
    1. Roxburgh CS, McMillan DC. Cancer and systemic inflammation: treat the tumour and treat the host. Br J Cancer. 2014;110(6):1409–1412.
    1. Aggerholm-Pedersen N, Maretty-Kongstad K, Keller J, Baerentzen S, Safwat A. The prognostic value of serum biomarkers in localized bone sarcoma. Transl Oncol. 2016;9(4):322–328.
    1. Ji H, Houghton AM, Mariani TJ, et al. K-ras activation generates an inflammatory response in lung tumors. Oncogene. 2006;25(14):2105–2112.
    1. Swierczak A, Mouchemore KA, Hamilton JA, Anderson RL. Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev. 2015;34(4):735–751.
    1. Lissoni P, Brivio F, Fumagalli L, et al. Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors. Int J Biol Markers. 2004;19(2):135–140.
    1. Li MX, Liu XM, Zhang XF, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2014;134(10):2403–2413.
    1. Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology. 2013;218(11):1402–1410.
    1. Ishii H, Takahara M, Nagato T, et al. Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer/T-cell lymphoma cells by cell contact-dependent interaction through membrane-bound IL-15. Int J Cancer. 2012;130(1):48–58.
    1. Ishikawa S, Miyashita T, Inokuchi M, et al. Platelets surrounding primary tumor cells are related to chemoresistance. Oncol Rep. 2016;36(2):787–794.
    1. Orellana R, Kato S, Erices R, et al. Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells. BMC Cancer. 2015;15:290.
    1. Sawant AC, Adhikari P, Narra SR, Srivatsa SS, Mills PK, Srivatsa SS. Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction. Cardiol J. 2014;21(5):500–508.
    1. Karaman M, Balta S, Seyit Ahmet AY, et al. The comparative effects of valsartan and amlodipine on vWf levels and N/L ratio in patients with newly diagnosed hypertension. Clin Exp Hypertens. 2013;35(7):516–522.
    1. Mocellin MC, Camargo CQ, Nunes EA, Fiates GM, Trindade EB. A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer. Clin Nutr. 2016;35(2):359–369.
    1. Mocellin MC, Pastore e Silva Jde A, Camargo Cde Q, et al. Fish oil decreases C-reactive protein/albumin ratio improving nutritional prognosis and plasma fatty acid profile in colorectal cancer patients. Lipids. 2013;48(9):879–888.

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