Asian Pacific Journal of Cancer Prevention

Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Are Neutrophil/Lymphocyte and Platelet/Lymphocyte Rates in Patients with Non-Small Cell Lung Cancer Associated with Treatment Response and Prognosis?

  • Unal, Dilek (Department of Radiation Oncology, Kayseri Education and Research Hospital) ;
  • Eroglu, Celalettin (Department of Radiation Oncology, Erciyes University Medical School) ;
  • Kurtul, Neslihan (Department of Radiation Oncology, Erciyes University Medical School) ;
  • Oguz, Arzu (Department of Medical Oncology, Kayseri Education and Research Hospital) ;
  • Tasdemir, Arzu (Department of Pathology, Kayseri Education and Research Hospital)
  • Published : 2013.09.30

Abstract

Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:${\geq}3.44$ and low:<194 or high${\geq}194$, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

Keywords

Neutrophil to lymphocyte ratio;non-small-cell lung cancer;platelet to lymphocyte ratio;prognosis

File

Download PDF

References

  1. Asher V, Lee J, Innamaa A, Bali A (2011). Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol, 13, 499-503. https://doi.org/10.1007/s12094-011-0687-9
  2. Coussens LM, Werb Z (2002). Inflammation and cancer. Nature, 420, 860-7. https://doi.org/10.1038/nature01322
  3. Assoian RK, Sporn MB (1986). Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol, 102, 1217-23. https://doi.org/10.1083/jcb.102.4.1217
  4. Cedres S, Torrejon D, Martinez A, et al (2012). Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol, 14, 864-9. https://doi.org/10.1007/s12094-012-0872-5
  5. Chua W, Charles KA, Baracos VE, Clarke SJ (2011). Neutrophil/ lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer, 104, 1288-95. https://doi.org/10.1038/bjc.2011.100
  6. Divella R, Daniele A, Savino E, et al (2013). Circulating levels of transforming growth factor-$\beta$ (TGF-$\beta$) and chemokine (C-X-C Motif) ligand-1 (CXCL1) as predictors of distant seeding of circulating tumor cells in patients with metastatic breast cancer. Anticancer Res, 33, 1491-7.
  7. Donskov F (2013). Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin Cancer Biol, 23, 200-7. https://doi.org/10.1016/j.semcancer.2013.02.001
  8. Dubernard V, Arbeille BB, Lemesle MB, Legrand C (1997). Evidence for an alpha-granular pool of the cytoskeletal protein alpha-actinin in human platelets that redistributes with the adhesive glycoprotein thrombospondin-1 during the exocytotic process. Arterioscler Thromb Vasc Biol, 17, 2293-305. https://doi.org/10.1161/01.ATV.17.10.2293
  9. Kaplan KL, Broekman MJ, Chernoff A, Lesznik GR, Drillings M (1979). Platelet alpha-granule proteins: studies on release and subcellular localization. Blood, 53, 604-18.
  10. Kaya MG, Akpek M, Lam YY, et al (2013). Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated myocardial infarction undergoing primary coronary intervention: A prospective, multicenter study. Int J Cardiol, 15, 1557-4.
  11. Negrier S, Escudier B, Gomez F, et al (2002). Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d'Immunotherapie. Ann Oncol, 13, 1460-8. https://doi.org/10.1093/annonc/mdf257
  12. Kobayashi N, Usui S, Kikuchi S, et al (2012). Preoperative lymphocyte count is an independent prognostic factor in node-negative non-small cell lung cancer. Lung Cancer, 75, 223-7. https://doi.org/10.1016/j.lungcan.2011.06.009
  13. Kocyigit I, Eroglu E, Unal A, et al (2013). Role of neutrophil/ lymphocyte ratio in prediction of disease progression in patients with stage-4 chronic kidney disease. J Nephrol, 26, 358-65. https://doi.org/10.5301/jn.5000152
  14. Majeti BK, Lee JH, Simmons BH, Shojaei F (2013). VEGF is an important mediator of tumor angiogenesis in malignant lesions in a genetically engineered mouse model of lung adenocarcinoma. BMC Cancer, 13, 213. https://doi.org/10.1186/1471-2407-13-213
  15. Paesmans M, Sculier JP, Libert P, et al (1995). Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. J Clin Oncol, 13, 1221-30. https://doi.org/10.1200/JCO.1995.13.5.1221
  16. Qian X, Tuszynski GP (1996). Expression of thrombospondin-1 in cancer: a role in tumor progression. Proc Soc Exp Biol Med, 212, 199-207. https://doi.org/10.3181/00379727-212-44008
  17. Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T (2012). Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol, 23, 265-73. https://doi.org/10.3802/jgo.2012.23.4.265
  18. Schmidt H, Bastholt L, Geertsen P, et al (2005). Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer, 93, 273-8. https://doi.org/10.1038/sj.bjc.6602702
  19. Stone RL, Nick AM, McNeish IA, et al (2012). Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med, 366, 610-8. https://doi.org/10.1056/NEJMoa1110352
  20. Teramukai S, Kitano T, Kishida Y, et al (2009). Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer, 45, 1950-8. https://doi.org/10.1016/j.ejca.2009.01.023
  21. Tomita M, Shimizu T, Ayabe T, Nakamura K, Onitsuka T (2012). Elevated preoperative inflammatory markers based on neutrophil-to-lymphocyte ratio and C-reactive protein predict poor survival in resected non-small cell lung cancer. Anticancer Res, 32, 3535-8.
  22. Wang D, Yang JX, Cao DY, et al (2013). Preoperative neutrophillymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma. Onco Targets Ther, 6, 211-6.
  23. Wang S, Zhang Z, Fang F, et al (2011). The neutrophil/ lymphocyte ratio is an independent prognostic indicator in patients with bone metastasis. Oncol Lett, 2, 735-40. https://doi.org/10.3892/ol.2011.304
  24. Yao Y, Yuan D, Liu H, Gu X, Song Y (2013). Pretreatment neutrophil to lymphocyte ratio is associated with response to therapy and prognosis of advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy. Cancer Immunol Immunother, 62, 471-9. https://doi.org/10.1007/s00262-012-1347-9
  25. Zhang J, Huang SH, Li H, et al (2013). Preoperative lymphocyte count is a favorable prognostic factor of disease-free survival in non-small-cell lung cancer. Med Oncol, 30, 352. https://doi.org/10.1007/s12032-012-0352-3

Cited by

  1. Predictive Role of the Neutrophil Lymphocyte Ratio for Invasion with Gestational Trophoblastic Disease vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4203
  2. Is the Combination of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios a Useful Predictor of Treatment Response and Prognosis in Patients with Non-Small Cell Lung Cancer? vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4373
  3. Treatment of Metastatic Colorectal Cancer With or Without Bevacizumab: Can the Neutrophil/Lymphocyte Ratio Predict the Efficiency of Bevacizumab? vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4781
  4. Mean Platelet Volume as a Prognostic Marker in Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Combined Chemotherapy vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6421
  5. Albumin-globulin Ratio for Prediction of Long-term Mortality in Lung Adenocarcinoma Patients vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6449
  6. Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6511
  7. Roles of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios in the Early Diagnosis of Malignant Ovarian Masses vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6881
  8. Radiosensitization Effect of Overexpression of Adenovirus-mediated SIRT6 on A549 Non-small Cell Lung Cancer Cells vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7297
  9. Expression of ERCC1, RRM1 and LRP in Non-small Cell Lung Cancers and their Influence on Chemotherapeutic Efficacy of Gemcitabine Concomitant with Nedaplatin vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7303
  10. Elevated Neutrophil-to-Lymphocyte Ratio in Squamous Cell Carcinoma of Larynx Compared to Benign and Precancerous Laryngeal Lesions vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7351
  11. The Neutrophil to Lymphocyte Ratio has a High Negative Predictive Value for Pathologic Complete Response in Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7737
  12. Are Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios Associated with Endometrial Precancerous and Cancerous Lesions in Patients with Abnormal Uterine Bleeding? vol.15, pp.4, 2014, https://doi.org/10.7314/APJCP.2014.15.4.1689
  13. Could the Neutrophil to Lymphocyte Ratio be a Poor Prognostic Factor for Non Small Cell Lung Cancers? vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2089
  14. Pretreatment Neutrophil/Lymphocyte Ratio as a Prognostic Aid in Colorectal Cancer vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2647
  15. Elevated Serum Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Could be Useful in Lung Cancer Diagnosis vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2651
  16. Prognostic Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma Using Tyrosine Kinase Inhibitors vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3801
  17. Differentiation between benign and malignant ovarian masses in the preoperative period using neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios vol.3, pp.2, 2014, https://doi.org/10.3892/mco.2014.481
  18. Prognostic Value of PLR in Various Cancers: A Meta-Analysis vol.9, pp.6, 2014, https://doi.org/10.1371/journal.pone.0101119
  19. Elevated Preoperative Platelet to Lymphocyte Ratio Associated with Decreased Survival of Women with Ovarian Clear Cell Carcinoma vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10831
  20. Relations of Platelet Indices with Endometrial Hyperplasia and Endometrial Cancer vol.16, pp.12, 2015, https://doi.org/10.7314/APJCP.2015.16.12.4905
  21. Evaluation of Inflammation Parameters in Philadelphia Negative Chronic Myeloproliferative Neoplasia Patients vol.16, pp.13, 2015, https://doi.org/10.7314/APJCP.2015.16.13.5159
  22. Prognostic Value of Baseline Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Local and Advanced Gastric Cancer Patients vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5933
  23. Prognostic Significance of Preoperative Anemia, Leukocytosis and Thrombocytosis in Chinese Women with Epithelial Ovarian Cancer vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.933
  24. Utility of Peripheral Blood Parameters in Predicting Breast Cancer Risk vol.16, pp.6, 2015, https://doi.org/10.7314/APJCP.2015.16.6.2409
  25. Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3997
  26. Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy vol.29, pp.5, 2015, https://doi.org/10.1111/dote.12322
  27. Usefulness of the neutrophil-to-lymphocyte ratio in predicting lymph node metastasis in patients with non-small cell lung cancer vol.36, pp.10, 2015, https://doi.org/10.1007/s13277-015-3462-7
  28. Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2833-9
  29. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis vol.5, pp.1, 2015, https://doi.org/10.1038/srep12493
  30. Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients vol.6, pp.3, 2015, https://doi.org/10.1111/1759-7714.12178
  31. Pretreatment Neutrophil to Lymphocyte Ratio Is Associated with Poor Survival in Patients with Stage I-III Non-Small Cell Lung Cancer vol.11, pp.10, 2016, https://doi.org/10.1371/journal.pone.0163397
  32. Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer vol.128, pp.17-18, 2016, https://doi.org/10.1007/s00508-015-0724-8
  33. Prognostic value of preoperative inflammatory response biomarkers in patients with esophageal cancer who undergo a curative thoracoscopic esophagectomy vol.16, pp.1, 2016, https://doi.org/10.1186/s12893-016-0179-5
  34. Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma vol.21, pp.5, 2016, https://doi.org/10.1007/s10147-016-0986-9
  35. Prognostic performance of inflammation-based prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy vol.4, pp.5, 2016, https://doi.org/10.3892/mco.2016.796
  36. The neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with peripheral T-cell lymphoma, unspecified vol.57, pp.1, 2016, https://doi.org/10.3109/10428194.2015.1045897
  37. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: a systematic review and meta-analysis vol.6, pp.1, 2016, https://doi.org/10.1038/srep22618
  38. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients vol.6, pp.1, 2016, https://doi.org/10.1038/srep23893
  39. Pretreatment Neutrophil-to-Lymphocyte Ratio and Lymphocyte Recovery vol.39, pp.7, 2017, https://doi.org/10.1097/MPH.0000000000000911
  40. Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction of Hepatocellular Carcinoma after Curative Liver Resection vol.XX, pp.XX, 2017, https://doi.org/10.14218/JCTH.2016.00035
  41. Neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, neutrophil–platelet score and prognostic nutritional index: do they have prognostic significance in metastatic pancreas cancer? pp.1473-4877, 2017, https://doi.org/10.1080/03007995.2017.1408579
  42. Platelet-to-lymphocyte ratio predicts the prognosis of patients with non-small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy pp.17597706, 2017, https://doi.org/10.1111/1759-7714.12547
  43. Prognostic value of combined platelet, fibrinogen, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with lung adenosquamous cancer vol.14, pp.4, 2017, https://doi.org/10.3892/ol.2017.6660
  44. Value of neutrophil-to-lymphocyte ratio for predicting lung cancer prognosis: A meta-analysis of 7,219 patients vol.7, pp.3, 2017, https://doi.org/10.3892/mco.2017.1342
  45. Survival and prognostic analysis of preoperative inflammatory markers in patients undergoing surgical resection for laryngeal squamous cell carcinoma vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4730-x
  46. Relationship between Inflammatory and Biological Markers and Lung Cancer vol.7, pp.7, 2018, https://doi.org/10.3390/jcm7070160
  47. Hematologic Markers as Prognostic Factors in Nonmetastatic Esophageal Cancer Patients under Concurrent Chemoradiotherapy vol.2019, pp.2314-6141, 2019, https://doi.org/10.1155/2019/1263050
  48. Serum biomarkers in patients with stable and acute exacerbation of chronic obstructive pulmonary disease: A comparative study vol.0, pp.0, 2019, https://doi.org/10.2478/jomb-2018-0050