Skip to main content
Log in

Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Recent evidence indicates that inflammation is an essential component of pathogenesis and progression of cancer. In this study, we analysed two indexes of systemic inflammation, the neutrophil–lymphocyte ratio (NLR) and platelet—lymphocyte ratio (PLR), with disease-free survival (DFS) and overall survival (OS) in liver-only colorectal metastases treated with liver resection following neoadjuvant chemotherapy. In this retrospective study, 140 patients were enroled. The NLR and PLR were calculated on the basis of preoperative blood cell count, and their cut-off levels were determined by applying receiver operating curve analysis. A NLR >2.4 and a PLR >150 were considered to be elevated. DFS and OS were calculated using both Kaplan–Meier and multivariate Cox regression methods. Both high NLR and high PLR were associated with decreased DFS [HR 1.55; 95 % confidence interval (CI) 1.03–2.32; P = 0.033, and HR 1.78; 95 % CI 1.19–2.67; P = 0.005, respectively] and OS (HR 2.21; 95 % CI 1.24–3.96; P = 0.007, and HR 2.90; 95 % CI 1.61–5.21; P < 0.001, respectively) in univariate analysis, but only PLR remained significant in multivariate analysis for both DFS and OS (HR 1.68; 95 % CI 1.04–2.71; P = 0.034, and HR 2.17; 95 % CI 1.09–4.32; P = 0.027, respectively). When we divided patients into three groups (group 1: normal both NLR and PLR; group 2: high NLR or high PLR; group 3: high both NLR and PLR), the five-year DFS and OS rates for these groups were 43, 26, 9 % (P = 0.004) and 73, 59, 34 % (P < 0.001), respectively. In this study, we indicate that preoperative PLR is superior to preoperative NLR as an adverse prognostic factor in patients who undergo liver resection for liver-only colorectal metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Geoghegan JG, Scheele J. Treatment of colorectal liver metastases. Br J Surg. 1999;86:158–69.

    Article  PubMed  CAS  Google Scholar 

  2. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D’Angelica M. Actual 10- year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;10(25):4575–80.

    Article  Google Scholar 

  3. Neal CP, Garcea G, Doucas H, Manson MM, Sutton CD, Dennison AR, Berry DP. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer. 2006;42:1728–43.

    Article  PubMed  CAS  Google Scholar 

  4. Tanaka K, Shimada H, Fujii Y, Endo I, Sekido H, Togo S, Ike H. Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver. Arch Surg. 2004;389:371–9.

    Article  Google Scholar 

  5. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of, 1001 consecutive cases. Ann Surg. 1999;230:309–21.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.

    Article  PubMed  CAS  Google Scholar 

  7. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Ramadori G, Van Damme J, Rieder H. Meyer zum Buschenfelde KH. Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. Eur J Immunol. 1998;18:1259–64.

    Article  Google Scholar 

  9. Ohsugi Y. Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases. Biol Pharm Bull. 2007;30:2001–6.

    Article  PubMed  CAS  Google Scholar 

  10. Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Kubota K. Preoperative thrombocytosis is associated with survival after surgery for colorectal cancer. J Surg Oncol. 2012;106:887–91.

    Article  PubMed  Google Scholar 

  11. Bhatti I, Peacock O, Lloyd G, Larvin M, Hall RI. Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am J Surg. 2010;200:197–203.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Silvis SE, Turkbas N, Doscherholmen A. Thrombocytosis in patients with lung cancer. JAMA. 1970;211:1852–3.

    Article  PubMed  CAS  Google Scholar 

  14. Monreal M, Fernandez-Llamazares J, Pinol M, Julian JF, Broggi M, Escola D, Abad A. Platelet count and survival in patients with colorectal cancer: a preliminary study. Thromb Haemost. 1998;79:916–8.

    PubMed  CAS  Google Scholar 

  15. Shimada H, Oohira G, Okazumi S, Matsubara H, Nabeya Y, Hayashi H, Takeda A, Gunji Y, Ochiai T. Thrombocytosis associated with poor prognosis in patients with oesophageal carcinoma. J Am Coll Surg. 2004;198:737–41.

    Article  PubMed  Google Scholar 

  16. Szkandera J, Pichler M, Absenger G, Stotz M, Arminger F, Weissmueller M, Schaberl-Moser R, Samonigg H, Kornprat P, Stojakovic T, Avian A, Gerger A. The elevated preoperative platelet to lymphocyte ratio predicts decreased time to recurrence in colon cancer patients. Am J Surg. 2014;208:210–4.

    Article  PubMed  Google Scholar 

  17. Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, Samonigg H, Stojakovic T, Gerger A. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer. 2014;110:435–40.

    Article  PubMed  CAS  Google Scholar 

  18. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48.

    Article  PubMed  CAS  Google Scholar 

  19. Hoffmann TK, Dworacki G, Tsukihiro T, Meidenbauer N, Gooding W, Johnson JT, Whiteside TL. Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res. 2002;8:2553–62.

    PubMed  Google Scholar 

  20. Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.

    Article  PubMed  CAS  Google Scholar 

  21. Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, Kudoh S, Ochiai A. Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113:1387–95.

    Article  PubMed  CAS  Google Scholar 

  22. Corthay A. Does the immune system naturally protect against cancer? Front Immunol. 2014;5:197.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, Vimond N, Concha A, Garrido F, Isambert N, Chaigneau L, Le Brun-Ly V, Dubreuil P, Cremer I, Caignard A, Poirier-Colame V, Chaba K, Flament C, Halama N, Jäger D, Eggermont A, Bonvalot S, Commo F, Terrier P, Opolon P, Emile JF, Coindre JM, Kroemer G, Chaput N, Le Cesne A, Blay JY, Zitvogel L. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2013;73:3499–510.

    Article  PubMed  CAS  Google Scholar 

  24. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and treatment Of cancer, National cancer Institute of the United States, National cancer Institute of Canada. J Natl Cancer Inst. 2000;2(92):205–16.

    Article  Google Scholar 

  25. Wong VK, Malik HZ, Hamady ZZ, Al-Mukhtar A, Gomez D, Prasad KR, Toogood GJ, Lodge JP. C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases. Br J Cancer. 2007;96:222–5.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Halazun KJ, Aldoori A, Malik HZ, Al-Mukhtar A, Prasad KR, Toogood GJ, Lodge JP. Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol. 2008;34:55–60.

    Article  PubMed  CAS  Google Scholar 

  27. Nakagawa K, Tanaka K, Nojiri K, Kumamoto T, Takeda K, Ueda M, Endo I. The modified Glasgow prognostic score as a predictor of survival after hepatectomy for colorectal liver metastases. Ann Surg Oncol. 2014;21:1711–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol. 2012;23:265–73.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.

    Article  PubMed  Google Scholar 

  30. Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, Ghaneh P. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.

    Article  PubMed  Google Scholar 

  31. Kwon HC, Kim SH, Oh SY, Lee S, Lee JH, Choi HJ, Park KJ, Roh MS, Kim SG, Kim HJ, Lee JH. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17:216–22.

    Article  PubMed  CAS  Google Scholar 

  32. 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.

    PubMed  Google Scholar 

  33. 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;30:439.

    Article  PubMed  Google Scholar 

  34. Jenne CN, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol. 2013;35:254–61.

    Article  PubMed  CAS  Google Scholar 

  35. Egan K, Crowley D, Smyth P, O’Toole S, Spillane C, Martin C, Gallagher M, Canney A, Norris L, Conlon N, McEvoy L, Ffrench B, Stordal B, Keegan H, Finn S, McEneaney V, Laios A, Ducrée J, Dunne E, Smith L, Berndt M, Sheils O, Kenny D, O’Leary J. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells. PLoS One. 2011;6:e26125.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Suzuki K, Aiura K, Ueda M, Kitajima M. The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents. Pancreas. 2004;29:132–40.

    Article  PubMed  CAS  Google Scholar 

  37. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33.

    Article  PubMed  CAS  Google Scholar 

  38. Sun B, Karin M. The therapeutic value of targeting inflammation in gastrointestinal cancers. Trends Pharmacol Sci. 2014;35:349–57.

    Article  PubMed  CAS  Google Scholar 

  39. Yamauchi T, Watanabe M, Hasegawa H, Nishibori H, Ishii Y, Tatematsu H, Yamamoto K, Kubota T, Kitajima M. The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer. Anticancer Res. 2003;23:245–9.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by the National Institute for Health Research Royal Marsden/Institute for Cancer Research Biomedical Research Centre.

Conflict of interest

All the authors of the paper declare no conflict of interest related to the present research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyriakos Neofytou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Neofytou, K., Smyth, E.C., Giakoustidis, A. et al. Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med Oncol 31, 239 (2014). https://doi.org/10.1007/s12032-014-0239-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0239-6

Keywords

Navigation