The Position of Neutrophils-To-Lymphocytes and Lymphocytes-To-Platelets Ratio as Predictive Markers of Progression and Prognosis in Patients with Non-Small Cell Lung Cancer

Plamen Minkov; Maya Gulubova; Petar Chilingirov; Julian Ananiev

doi:10.3889/oamjms.2018.210

Authors

Plamen Minkov Trakia University, Stara Zagora
Maya Gulubova Department of General and Clinical Pathology, Forensic Medicine and Deontology, Trakia University, Stara Zagora
Petar Chilingirov Trakia University, Stara Zagora
Julian Ananiev Department of General and Clinical Pathology, Forensic Medicine and Deontology, Trakia University, Stara Zagora

DOI:

https://doi.org/10.3889/oamjms.2018.210

Keywords:

Lung cancer, NLR, PLR, Prognosis

Abstract

BACKGROUND: Non-small cell lung cancer (NSCLC) is an insidious metastasis condition of the lungs often presenting no symptoms at the onset. Defining markers for quick determination of prognosis is essential for building up a treatment strategy.

AIM: The aim of this study is to define the role of the Neutrophils-to-Lymphocytes ratio (NLR) and Platelets-to- Lymphocytes ratio (PLR) as biomarkers in patients with NSCLC, according to the stage and prognosis of the disease.

METHODS: We investigated 20 patients with NSCLC. NLR and PLR are calculated and are evaluated according to the presence or absence of metastasis, stage of the disease, histological type and survival rate.

RESULTS: We found that thirteen of the patients had low NLR, while the rest 7 had high NLR (mean 3.15). By analysing PLR we found that 11 patients have low and 9 have high level of PLR (mean 1.42). After the correlations have been made we discovered that in 90.1% of the patients with low PLR no lymph metastasises were detected, while in 50% of the patients with high PLR lymph metastasises were observed (c2 = 3.99; P = 0.046). We also discovered that in 84.6% of the patients with low NLR lymph metastases were absent, while in 42.9% with high NLR lymph metastasises were present (c 2 = 1.83; P = 0.176).

CONCLUSION: In conclusion, NLR and PLR were discovered as prominent biomarkers which provide relatively fast determination for prognosis in patients with NSCLC.

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References

Siegel R, Naishadham D, Jemal A. Cancer statistics. 2013. CA Cancer J Clin. 2013; 63(1):11-30. https://doi.org/10.3322/caac.21166

Albain KS, Swann RS, Rusch VW, Turrisi III AT, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. The Lancet. 2009; 374(9687):379-86. https://doi.org/10.1016/S0140-6736(09)60737-6

Riquet M, Bagan P, Barthes FL, Banu E, Scotte F, Foucault C, Dujon A, Danel C. Completely resected non-small cell lung cancer: reconsidering prognostic value and significance of N2 metastases. The Annals of thoracic surgery. 2007; 84(6):1818-24. https://doi.org/10.1016/j.athoracsur.2007.07.015

Simon GR, Sharma S, Cantor A, Smith P, Bepler G. ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest. 2005; 127(3):978-83. https://doi.org/10.1378/chest.127.3.978

Hoang T, Xu R, Schiller JH, Bonomi P, Johnson DH. Clinical model to predictsurvival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapyregimens based on eastern cooperative oncology group data. J Clin Oncol. 2005; 23(1):175-83. https://doi.org/10.1200/JCO.2005.04.177 PMid:15625371

Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 2013; 382: 720-731. https://doi.org/10.1016/S0140-6736(13)61715-8

Molina JR, Yang P, Cassivi SD, Schild SE, Adjei A. Non-small cell lung cancer: epidemiology. risk factors. treatment. and survivorship. Mayo Clin Proc. 2008; 83(5):584-94. https://doi.org/10.1016/S0025-6196(11)60735-0

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. https://doi.org/10.1016/j.cell.2011.02.013

Grivennikov SI. Greten FR. Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. https://doi.org/10.1016/j.cell.2010.01.025 PMid:20303878 PMCid:PMC2866629

Mantovani A. Allavena P. Sica A. Balkwill F. Cancer-related inflammation. Nature. 2008; 454(7203):436-44. https://doi.org/10.1038/nature07205 PMid:18650914

Aerts JG. Hegmans JP. Tumor-specific cytotoxic T cells are crucial for efficacy of immunomodulatory antibodies in patients with lung cancer. Cancer Res. 2013; 73(8):2381-8. https://doi.org/10.1158/0008-5472.CAN-12-3932

Vermaelen K. Pauwels R. Pulmonary dendritic cells. Am J Respir Crit Care Med. 2005; 172(5):530-51. https://doi.org/10.1164/rccm.200410-1384SO

Tartour E. Zitvogel L. Lung cancer: potential targets for immunotherapy. Lancet Respir Med. 2013; 1:551-63. https://doi.org/10.1016/S2213-2600(13)70159-0

Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003; 290(16):2149-58. https://doi.org/10.1001/jama.290.16.2149

Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med. 1998; 188(2):341-50. https://doi.org/10.1084/jem.188.2.341

Rogler G. Chronic ulcerative colitis and colorectal cancer. Cancer Lett. 2014; 345(2):235-41. https://doi.org/10.1016/j.canlet.2013.07.032

van Egmond M. Bakema JE. Neutrophils as effector cells for antibody-based immunotherapy of cancer. Semin Cancer Biol. 2013; 23(3):190-9. https://doi.org/10.1016/j.semcancer.2012.12.002

Jin H. Zhang G. Liu X. Liu X. Chen C. Yu H. Huang X. Zhang Q. Yu J. Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol. 2013; (11):112. https://doi.org/10.1186/1477-7819-11-112

Sagiv JY, Michaeli J, Assi S, Mishalian I, Kisos H, Levy L, Damti P, Lumbroso D, Polyansky L, Sionov RV, Ariel A, Hovav AH, Henke E, Fridlender ZG, Granot Z. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015; 10(4):562-73. https://doi.org/10.1016/j.celrep.2014.12.039 PMid:25620698

Sionov RV, Fridlender ZG, Granot Z. The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment. Cancer Microenviron. 2015; 8(3):125-58. https://doi.org/10.1007/s12307-014-0147-5 PMCid:PMC4714999

Unsal E, Atalay F, Atikcan S, Yilmaz A. Prognostic significance of hemostatic parameters in patients with lung cancer. Respir Med. 2004; 98(2):93-8. https://doi.org/10.1016/j.rmed.2003.07.001

Komurcuoglu B, Ulusoy S, Gayaf M, Guler A, Ozden E. Prognostic value of plasma D-dimer levels in lung carcinoma. Tumori. 2011; 97(6):743-8. https://doi.org/10.1177/030089161109700611 PMid:22322841

Van Doormaal FF, Raskob GE, Davidson BL, Decousus H, Gallus A, Lensing AW, Piovella F, Prins MH, B?ller HR. Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. Thromb Haemost. 2009; 101(4):762-9. https://doi.org/10.1160/TH08-09-0563

Gonzalez Barcala FJ, Garcia Prim JM. Platelet count: association with prognosis in lung cancer. Med Oncol. 2010; 27:357-62. https://doi.org/10.1007/s12032-009-9217-9

Aoe K, Hiraki A, Ueoka H. Thrombocytosis as a useful prognostic indicator in patients with lung cancer. Respiration. 2004; 71:170-3. https://doi.org/10.1159/000076679

Gislason T, Nu E. Sedimentation rate. leucocytes. platelet count and hemoglobin in bronchial carcinoma: an epidemiological study. Eur J Respir Dis. 1985; 66:141-6.

Pedersen LM, Milman N. Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respir J. 1996; 9:1826-30. https://doi.org/10.1183/09031936.96.09091826

Cox G, Walker RA, Andi A. Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer. Lung Cancer. 2000; 29:169-77. https://doi.org/10.1016/S0169-5002(00)00124-0

Schreiber RD. Old LJ. Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. https://doi.org/10.1126/science.1203486

Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010; 6(1):149-63. https://doi.org/10.2217/fon.09.136

Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. Walsh J Surg Oncol. 2005; 91(3):181-4. https://doi.org/10.1002/jso.20329 PMid:16118772

Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, et al. Usefulness of the neutrophil-to -lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012; 19(1):217-24. https://doi.org/10.1245/s10434-011-1814-0

Gwak MS, Choi SJ, Kim JA, Ko JS, Kim TH, Lee SM, et al. Effects of gender on white blood cell populations and neutrophil-lymphocyte ratio following gastrectomy in patients with stomach cancer. J Korean Med Sci. 2007; 22(Suppl):S104-8. https://doi.org/10.3346/jkms.2007.22.S.S104 PMid:17923734

Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, Kornprat P, AlZoughbi W, Seggewies FS, Lackner C, Stojakovic T, Samonigg H, Hoefler G, Pichler M. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013; 109(2):416-21. https://doi.org/10.1038/bjc.2013.332

Sharaiha RZ, Halazun KJ, Mirza F, Port JL, Lee PC, Neugut AI, et al. Elevated preoperative neutrophil: lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011; 18(12):3362-9. https://doi.org/10.1245/s10434-011-1754-8 PMCid:PMC3192937

Yin Y. Wang J, Wang X, Gu L, Pei H, Kuai S, Zhang Y, Shang Z. Clinics (Sao Paulo). 2015; 70(7):524-530. https://doi.org/10.6061/clinics/2015(07)10

Aliustaoglu M, Bilici A, Ustaalioglu BB, Konya V, Gucun M, Seker M, Gumus M. The effect of peripheral blood values on prognosis of patients with locally advanced gastric cancer before treatment. Med Oncol. 2010; 27(4):1060-5. https://doi.org/10.1007/s12032-009-9335-4

Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S, Habeshy A, Picon A, Bloom S. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 2013; 30(1):432. https://doi.org/10.1007/s12032-012-0432-4

He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, Chen X, Rong R, Zhang B, Xia L. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013; 30(1):439. https://doi.org/10.1007/s12032-012-0439-x

Liu H, Wu Y, Wang Z, Yao Y, Chen F, Zhang H, Wang Y, Song Y. Pretreatment platelet-to-lymphocyte ratio (PLR) as a predictor of response to first-line platinum-based chemotherapy and prognosis for patients with non-small cell lung cancer. J Thorac Dis. 2013; 5(6):783-9.

Cannon NA, Meyer J, Iyengar P, Ahn C, Westover KD, Choy H. Timmerman R. Neutrophil-lymphocyte and platelet-lymphocyte ratios as prognostic factors after stereotactic radiation therapy for early-stage non-small-cell lung cancer. J Thorac Oncol. 2015; 10(2):280-5. https://doi.org/10.1097/JTO.0000000000000399 PMid:25299234

Pinato DJ, Shiner RJ, Seckl MJ, Stebbing J, Sharma R, Mauri FA. Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. Br J Cancer. 2014; 110(8):1930-5. https://doi.org/10.1038/bjc.2014.145 PMCid:PMC3992503

Wu G, Yao Y, Bai C, Zeng J, Shi D, Gu X, Shi X, Song Y. Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. Thorac Cancer. 2015; 6(3):275-87. https://doi.org/10.1111/1759-7714.12178 PMid:26273373

Douillard JY, Shepherd FA, Hirsh V, Mok T, Socinski MA, Gervais R, Liao ML, Bischoff H, Reck M, Sellers MV, Watkins CL, Speake G, Armour AA, Kim ES. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol. 2010; 28(5):744-52. https://doi.org/10.1200/JCO.2009.24.3030

Kemal Y, Yucel I, Ekiz K, Demirag G, Yilmaz B, Teker F, Ozdemir M. Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis. Asian Pac J Cancer Prev. 2014; 15(6):2651-4. https://doi.org/10.7314/APJCP.2014.15.6.2651

Wang L, Liang D, Xu X, Jin J, Li S, Tian G, Gao Z, Liu C, He Y. The prognostic value of neutrophil to lymphocyte and platelet to lymphocyte ratios for patients with lung cancer. Oncol Lett. 2017; 14(6):6449-6456. https://doi.org/10.3892/ol.2017.7047

Liu D, Huang Y, Li L, Song J, Zhang L, Li W. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer. 2017; 17(1):882. https://doi.org/10.1186/s12885-017-3893-1

Liu D, Jin J, Zhang L, Li L, Song J, Li W. The Neutrophil to Lymphocyte Ratio May Predict Benefit from Chemotherapy in Lung Cancer. Cell Physiol Biochem. 2018; 46(4):1595-1605. https://doi.org/10.1159/000489207 PMid:29694985

Kang MH, Go SI, Song HN, Lee A, Kim SH, Kang JH, Jeong BK, Kang KM, Ling H, Lee GW. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer. 2014; 111(3):452-60. https://doi.org/10.1038/bjc.2014.317

Unal D, Eroglu C, Kurtul N, Oguz A, Tasdemir A. Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis? Asian Pac J Cancer Prev. 2013; 14(9):5237-42. https://doi.org/10.7314/APJCP.2013.14.9.5237 PMid:24175807

Zhang H, Gao L, Zhang B, Zhang L, Wang C. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis. Sci Rep. 2016; (6):22618. https://doi.org/10.1038/srep22618 PMid:26939789

Gu XB, Tian T, Tian XJ, Zhang XJ. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis. Sci Rep. 2015; (5):12493. https://doi.org/10.1038/srep12493 PMid:26205001 PMCid:PMC4513342

Pinato DJ, Shiner RJ, Seckl MJ, Stebbing J, Sharma R, Mauri FA. Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. British Journal of Cancer. 2014; 110(8):1930-1935. https://doi.org/10.1038/bjc.2014.145