Advertisement

Tumor Biology

, Volume 35, Issue 11, pp 11659–11666 | Cite as

The preoperative lymphocyte to monocyte ratio predicts clinical outcomes in patients with stage II/III gastric cancer

  • Xin Zhou
  • Yiping Du
  • Jun Xu
  • Zebo Huang
  • Tianzhu Qiu
  • Xiaping Wang
  • Jiaqi Qian
  • Wei Zhu
  • Ping Liu
Research Article

Abstract

Recently, lymphocyte to monocyte ratio (LMR) has been reported to be associated with clinical outcomes in some types of cancer but has not been explored in gastric cancer. In this study, we analyzed the association between LMR and clinical outcomes in stage II/III gastric cancer patients. Preoperative LMR calculated from peripheral lymphocyte and monocyte with corresponding clinical features from 426 stage II/III gastric cancer patients was noted. Kaplan–Meier method and Cox regression model were applied for overall survival (OS) and recurrence-free survival (RFS). Related with smaller tumor size (p < 0.001), increased LMR could predict better OS [hazard ratio (HR), 0.688; 95 % confidence interval (CI), 0.521–0.908, p = 0.008] and was borderline significantly associated with better RFS (HR, 0.775; 95 % CI, 0.592–1.01, p = 0.06) in stage II/III gastric cancer patients through multivariable analysis. Subgroup analyses revealed that except stage III patients for RFS which yielded borderline significance (p = 0.052), lower LMR was associated with poor clinical outcomes for patients regardless of different stages or whether the patients received adjuvant chemotherapy. The elevated preoperative LMR level was a significant favorable factor in the prognosis of stage II/III gastric cancer patients, especially for those with stage II. However, further validation of our findings is warranted.

Keywords

LMR Gastric cancer Prognosis 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant number: 81171908).

Conflicts of interest

None

References

  1. 1.
    Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol WJG. 2006;12:354–62.Google Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  3. 3.
    Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (expand): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–9.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.PubMedCrossRefGoogle Scholar
  7. 7.
    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Jiang X, Hiki N, Nunobe S, Kumagai K, Kubota T, Aikou S, et al. Prognostic importance of the inflammation-based Glasgow prognostic score in patients with gastric cancer. Br J Cancer. 2012;107:275–9.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Cho IR, Park JC, Park CH, Jo JH, Lee HJ, Kim S, Shim CN, Lee H, Shin SK, Lee SK, Lee YC: Pre-treatment neutrophil to lymphocyte ratio as a prognostic marker to predict chemotherapeutic response and survival outcomes in metastatic advanced gastric cancer. Gastric Cancer. 2014. doi:  10.1007/s10120-013-0330-2.
  10. 10.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Shimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, et al. High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer. 2010;13:170–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Li ZM, Huang JJ, Xia Y, Sun J, Huang Y, Wang Y, et al. Blood lymphocyte-to-monocyte ratio identifies high-risk patients in diffuse large B-cell lymphoma treated with R-CHOP. PLoS One. 2012;7:e41658.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Porrata LF, Ristow K, Colgan JP, Habermann TM, Witzig TE, Inwards DJ, et al. Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin’s lymphoma. Haematologica. 2012;97:262–9.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer. 2014;110:435–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Li J, Jiang R, Liu WS, Liu Q, Xu M, Feng QS, et al. A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma. PLoS One. 2013;8:e83069.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.PubMedCrossRefGoogle Scholar
  17. 17.
    Penta R, De Falco M, Iaquinto G, De Luca A. Helicobacter pylori and gastric epithelial cells: from gastritis to cancer. J Exp Clin Cancer Res CR. 2005;24:337–45.Google Scholar
  18. 18.
    Sun B, Karin M. Obesity, inflammation, and liver cancer. J Hepatol. 2012;56:704–13.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353:2654–66.PubMedCrossRefGoogle Scholar
  22. 22.
    Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS, et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol. 2007;25:2586–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007;104:3967–72.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee HE, Chae SW, Lee YJ, Kim MA, Lee HS, Lee BL, et al. Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer. Br J Cancer. 2008;99:1704–11.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Wakatsuki K, Sho M, Yamato I, Takayama T, Matsumoto S, Tanaka T, et al. Clinical impact of tumor-infiltrating CD45RO+ memory T cells on human gastric cancer. Oncol Rep. 2013;29:1756–62.PubMedGoogle Scholar
  27. 27.
    Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18–32.PubMedCrossRefGoogle Scholar
  28. 28.
    Perrone G, Ruffini PA, Catalano V, Spino C, Santini D, Muretto P, et al. Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. Eur J Cancer. 2008;44:1875–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Sinicrope FA, Rego RL, Ansell SM, Knutson KL, Foster NR, Sargent DJ. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology. 2009;137:1270–9.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, et al. Increased regulatory t cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132:2328–39.PubMedCrossRefGoogle Scholar
  31. 31.
    Yu P, Fu YX. Tumor-infiltrating T lymphocytes: friends or foes? Laboratory investigation. J Tech Methods Pathol. 2006;86:231–45.CrossRefGoogle Scholar
  32. 32.
    Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, et al. Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer. Oncol Rep. 2011;25:1271–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Amedei A, Della Bella C, Silvestri E, Prisco D, D’Elios MM. T cells in gastric cancer: friends or foes. Clin Dev Immunol. 2012;2012:690571.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383–91.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    De Giorgi U, Mego M, Scarpi E, Giuliano M, Giordano A, Reuben JM, et al. Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer. Clin Breast Cancer. 2012;12:264–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Tsavaris N, Baxevanis C, Kosmidis P, Papamichael M. The prognostic significance of immune changes in patients with renal cancer, melanoma and colorectal cancer, treated with interferon alpha 2b. Cancer Immunol Immunother CII. 1996;43:94–102.CrossRefGoogle Scholar
  37. 37.
    Fumagalli LA, Vinke J, Hoff W, Ypma E, Brivio F, Nespoli A. Lymphocyte counts independently predict overall survival in advanced cancer patients: a biomarker for IL-2 immunotherapy. J Immunother. 2003;26:394–402.PubMedCrossRefGoogle Scholar
  38. 38.
    Lissoni P, Brivio F, Fumagalli L, Messina G, Ghezzi V, Frontini 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;19:135–40.PubMedGoogle Scholar
  39. 39.
    Bruckner HW, Lavin PT, Plaxe SC, Storch JA, Livstone EM. Absolute granulocyte, lymphocyte, and monocyte counts. Useful determinants of prognosis for patients with metastatic cancer of the stomach. JAMA. 1982;247:1004–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Kitano S. Prognostic value of preoperative peripheral blood monocyte count in patients with hepatocellular carcinoma. Surgery. 2006;139:755–64.PubMedCrossRefGoogle Scholar
  41. 41.
    Lee YY, Choi CH, Sung CO, Do IG, Huh S, Song T, et al. Prognostic value of pre-treatment circulating monocyte count in patients with cervical cancer: comparison with SCC-Ag level. Gynecol Oncol. 2012;124:92–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Lin EY, Pollard JW. Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer. 2004;90:2053–8.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Xiong M, Elson G, Legarda D, Leibovich SJ. Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway. Am J Pathol. 1998;153:587–98.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Leek RD, Harris AL. Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia. 2002;7:177–89.PubMedCrossRefGoogle Scholar
  45. 45.
    Krstic J, Santibanez JF. Transforming growth factor-beta and matrix metalloproteinases: functional interactions in tumor stroma-infiltrating myeloid cells. Sci World J. 2014;2014:521754.CrossRefGoogle Scholar
  46. 46.
    Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253–68.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Diaz-Montero CM, Finke J, Montero AJ. Myeloid-derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications. Semin Oncol. 2014;41:174–84.PubMedCrossRefGoogle Scholar
  48. 48.
    Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18:1254–61.PubMedCrossRefGoogle Scholar
  49. 49.
    Arihara F, Mizukoshi E, Kitahara M, Takata Y, Arai K, Yamashita T, et al. Increase in CD14 + HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol Immunother CII. 2013;62:1421–30.CrossRefGoogle Scholar
  50. 50.
    Huang A, Zhang B, Wang B, Zhang F, Fan KX, Guo YJ. Increased CD14(+)HLA-DR (-/low) myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients. Cancer Immunol Immunother CII. 2013;62:1439–51.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xin Zhou
    • 1
  • Yiping Du
    • 1
  • Jun Xu
    • 1
  • Zebo Huang
    • 1
  • Tianzhu Qiu
    • 1
  • Xiaping Wang
    • 3
  • Jiaqi Qian
    • 1
  • Wei Zhu
    • 1
  • Ping Liu
    • 1
    • 2
  1. 1.Department of OncologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Cancer Center of Nanjing Medical UniversityNanjingChina
  3. 3.Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu ProvinceNanjing Medical UniversityNanjingChina

Personalised recommendations