Tumor Biology

, Volume 36, Issue 12, pp 9319–9325 | Cite as

Stage-dependent changes of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in colorectal cancer

  • Jing Jia
  • Xiongwei Zheng
  • Ying Chen
  • Lin Wang
  • Lu Lin
  • Xingming Ye
  • Yan Chen
  • Dedong Chen
  • Markus Dettke
Research Article

Abstract

This study aims to assess the association of the preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with tumor stage in colorectal cancer (CRC) patients. A retrospective study was performed in 336 CRC patients. Preoperative whole blood counts, serum levels of carcinoembryonic antigen (CEA), and clinicopathologic data were collected. The correlations between laboratory parameters and the tumor, node, and metastasis (TNM) stages were analyzed. The clinicopathologic TNM stages among CRC patients were 12.8 % at stage I, 32.4 % at stage II, 44.6 % at stage III, and 10.1 % at stage IV. NLR, PLR, and CEA levels were higher in CRC patients compared to healthy controls (all P < 0.0001). Both NLR and PLR showed an early elevation as compared to CEA, with a higher area under curve (AUC) value (0.71 vs. 0.62) in predicting the presence of the tumor with stage I/II. Accordingly, significant elevations of NLR (P = 0.0018) and PLR (P < 0.0001) were firstly detected in stage I and stage II, respectively. In addition, NLR exhibited a second phase elevation in stage IV, with a significant higher level in M1 subgroup compared to M0 subgroup (P = 0.022). While PLR showed a T stage-dependent increase (P = 0.0003) and was identified as an independent factor for the T grade development (P < 0.0001). Our data indicated that both neutrophil- and platelet-mediated inflammatory reactions are predominantly involved in the different stages of CRC development. Determination of pretreatment levels of NLR and PLR might provide useful information for the early diagnosis or the therapeutic choices in CRC patients.

Keywords

Colorectal cancer TNM stage Neutrophil to lymphocyte ratio Platelet to lymphocyte ratio 

Notes

Conflicts of interest

None

References

  1. 1.
    Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490–502.CrossRefPubMedGoogle Scholar
  2. 2.
    Dai Z, Zheng RS, Zou XN, Zhang SW, Zeng HM, Li N, et al. Analysis and prediction of colorectal cancer incidence trend in China. Zhonghua Yu Fang Yi Xue Za Zhi. 2012;46:598–603.PubMedGoogle Scholar
  3. 3.
    Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Swiderska M, Choromańska B, Dąbrowska E, Konarzewska-Duchnowska E, Choromańska K, Szczurko G, et al. The diagnostics of colorectal cancer. Contemp Oncol (Pozn). 2014;18:1–6.Google Scholar
  5. 5.
    Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:759–71.CrossRefPubMedGoogle Scholar
  7. 7.
    Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30:1073–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.CrossRefPubMedGoogle Scholar
  10. 10.
    Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23:1204–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2014;134:2403–13.CrossRefPubMedGoogle Scholar
  12. 12.
    Malietzis G, Giacometti M, Askari A, Nachiappan S, Kennedy RH, Faiz OD, et al. A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery. Ann Surg. 2014;260:287–92.CrossRefPubMedGoogle Scholar
  13. 13.
    Liu H, Du X, Sun P, Xiao C, Xu Y, Li R. Preoperative platelet-lymphocyte ratio is an independent prognostic factor for resectable colorectal cancer. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33:70–3.PubMedGoogle Scholar
  14. 14.
    Lee S, Oh SY, Kim SH, Lee JH, Kim MC, Kim KH, et al. Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy. BMC Cancer. 2013;13:350.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhou X, Du Y, Huang Z, Xu J, Qiu T, Wang J, et al. Prognostic value of PLR in various cancers: a meta-analysis. PLoS One. 2014;9, e101119.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chua W, Charles KA, Baracos VE, Clarke SJ. Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011;104:1288–95.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cannon NA, Meyer J, Iyengar P, Ahn C, Westover KD, Choy H, et al. Neutrophil-lymphocyte and platelet-lymphocyte ratios as prognostic factors following stereotactic radiation therapy for early-stage non-small cell lung cancer. J Thorac Oncol. 2015;10:280–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Mariani F, Sena P, Roncucci L. Inflammatory pathways in the early steps of colorectal cancer development. World J Gastroenterol. 2014;20:9716–31.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Grivennikov SI. Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol. 2013;35:229–44.CrossRefPubMedGoogle Scholar
  21. 21.
    Kilincalp S, Coban S, Akinci H, Hamamc M, Karaahmet F, Coşkun Y, et al. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma. Eur J Cancer Prev. 2014.Google Scholar
  22. 22.
    Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet-cancer loop. Eur J Intern Med. 2013;24:393–400.CrossRefPubMedGoogle Scholar
  23. 23.
    Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood. 2001;98:2720–5.CrossRefPubMedGoogle Scholar
  24. 24.
    van Rossum AP, Vlasveld LT, Vlasveld IN, Jansen PM, Dik WA, Hooijkaas H, et al. Granulocytosis and thrombocytosis in renal cell carcinoma: a pro-inflammatory cytokine response originating in the tumour. Neth J Med. 2009;67:191–4.PubMedGoogle Scholar
  25. 25.
    Goubran HA, Stakiw J, Radosevic M, Burnouf T. Platelet-cancer interactions. Semin Thromb Hemost. 2014;40:296–305.CrossRefPubMedGoogle Scholar
  26. 26.
    Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015.Google Scholar
  27. 27.
    He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013;30:439.CrossRefPubMedGoogle Scholar
  28. 28.
    Holmes CE, Levis JE, Ornstein DL. Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis. Clin Exp Metastasis. 2009;26:653–61.CrossRefPubMedGoogle Scholar
  29. 29.
    Radziwon-Balicka A, Santos-Martinez MJ, Corbalan JJ, O'Sullivan S, Treumann A, Gilmer JF, et al. Mechanisms of platelet-stimulated colon cancer invasion: role of clusterin and thrombospondin 1 in regulation of the P38MAPK-MMP-9 pathway. Carcinogenesis. 2014;35:324–32.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jing Jia
    • 1
  • Xiongwei Zheng
    • 1
  • Ying Chen
    • 1
  • Lin Wang
    • 1
  • Lu Lin
    • 1
  • Xingming Ye
    • 1
  • Yan Chen
    • 1
  • Dedong Chen
    • 1
  • Markus Dettke
    • 2
  1. 1.Fujian Provincial Cancer HospitalThe Affiliated Hospital of Fujian Medical UniversityFuzhouChina
  2. 2.Medical University of ViennaViennaAustria

Personalised recommendations