Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2015

Open Access 01-12-2015 | Research

Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer

Authors: Jing Chen, Dongsheng Hong, You Zhai, Peng Shen

Published in: World Journal of Surgical Oncology | Issue 1/2015

Login to get access

Abstract

Background

The prognostic role of inflammation indices, such as the neutrophil-to-lymphocyte ratio (NLR) in gastric cancer (GC) remains controversial. We conducted a meta-analysis to determine the predictable value of NLR in the clinical outcome of GC patients.

Methods

We searched Embase, PubMed and the Cochrane Library database for relevant randomised controlled trials. Statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals of overall survival (OS) and progression-free survival (PFS) using either random-effect or fixed-effect models according to the heterogeneity of the included studies. An analysis was carried out based on data from nine studies to evaluate the association between NLR and OS in patients with GC.

Results

Our analysis indicated that elevated pre-treatment NLR predicted poorer OS (HR: 2.16, 95% CI: 1.86 to 2.51, P < 0.001) and PFS (HR 2.78, 95% CI: 1.95 to 3.96; P < 0.00001) in patients with GC. Over a 3-year follow-up period, high NLR was a significant predictor of poor outcomes at year 1 (HR 1.99; 95% CI: 1.39 to 2.85; P = 0.0002), year 2 (HR 2.24; 95% CI: 1.69 to 2.97; P < 0.00001) and year 3 (HR 2.80; 95% CI: 1.98 to 3.96; P < 0.00001).

Conclusions

Elevated preoperative NLR is associated with poorer rates of survival in GC patients and may play a role in GC surveillance programmes as a means of delivering more personalised cancer care.
Appendix
Available only for authorised users
Literature
1.
go back to reference Zhu A, Sonnenberg A. Is gastric cancer again rising? J Clin Gastro. 2012;46:804–6.CrossRef Zhu A, Sonnenberg A. Is gastric cancer again rising? J Clin Gastro. 2012;46:804–6.CrossRef
2.
3.
go back to reference Peng CW, Wang LW, Zeng WJ, Yang XJ, Li Y. Evaluation of the staging systems for gastric cancer. J Surg Oncol. 2013;108:93–105.CrossRefPubMed Peng CW, Wang LW, Zeng WJ, Yang XJ, Li Y. Evaluation of the staging systems for gastric cancer. J Surg Oncol. 2013;108:93–105.CrossRefPubMed
4.
go back to reference MacDonald N. Cancer cachexia and targeting chronic inflammation: a unified approach to cancer treatment and palliative/supportive care. J Support Oncol. 2007;5:157–62.PubMed MacDonald N. Cancer cachexia and targeting chronic inflammation: a unified approach to cancer treatment and palliative/supportive care. J Support Oncol. 2007;5:157–62.PubMed
5.
go back to reference Yamashita H, Katai H. Systemic inflammatory response in gastric cancer. World J Surg. 2010;34:2399–400.CrossRefPubMed Yamashita H, Katai H. Systemic inflammatory response in gastric cancer. World J Surg. 2010;34:2399–400.CrossRefPubMed
6.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.CrossRefPubMed Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.CrossRefPubMed
7.
go back to reference Chua TC, Chong CH, Liauw W, Zhao J, Morris DL. Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy. Ann Surg. 2012;256:342–9.CrossRefPubMed Chua TC, Chong CH, Liauw W, Zhao J, Morris DL. Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy. Ann Surg. 2012;256:342–9.CrossRefPubMed
8.
go back to reference Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, et al. A comparison of inflammation-based prognostic scores in patients with cancer: a glasgow inflammation outcome study. Eur J Cancer. 2011;47:2633–41.CrossRefPubMed Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O'Reilly DS, et al. A comparison of inflammation-based prognostic scores in patients with cancer: a glasgow inflammation outcome study. Eur J Cancer. 2011;47:2633–41.CrossRefPubMed
9.
go back to reference Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.CrossRefPubMed Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.CrossRefPubMed
11.
go back to reference Zahorec R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102:5–14.PubMed Zahorec R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102:5–14.PubMed
12.
go back to reference Dirican A, Kucukzeybek BB, Alacacioglu A, Kucukzeybek Y, Erten C, Varol U, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer? Int J Clin Oncol. 2014;20:70–81.CrossRefPubMed Dirican A, Kucukzeybek BB, Alacacioglu A, Kucukzeybek Y, Erten C, Varol U, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer? Int J Clin Oncol. 2014;20:70–81.CrossRefPubMed
13.
go back to reference Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013;58:58–64.CrossRefPubMed Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013;58:58–64.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference Li QQ, Lu ZH, Yang L, Lu M, Zhang XT, Li J, et al. Neutrophil count and the inflammation-based glasgow prognostic score predict survival in patients with advanced gastric cancer receiving first-line chemotherapy. Asian Pac J Cancer Prev. 2014;15:945–50.CrossRefPubMed Li QQ, Lu ZH, Yang L, Lu M, Zhang XT, Li J, et al. Neutrophil count and the inflammation-based glasgow prognostic score predict survival in patients with advanced gastric cancer receiving first-line chemotherapy. Asian Pac J Cancer Prev. 2014;15:945–50.CrossRefPubMed
18.
go back to reference Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.CrossRefPubMed Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.CrossRefPubMed
19.
go back to reference Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedCentralPubMed Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedCentralPubMed
20.
go back to reference Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2007;73:215–20.CrossRefPubMed Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2007;73:215–20.CrossRefPubMed
21.
go back to reference Mohri Y, Tanaka K, Ohi M, Yokoe T, Miki C, Kusunoki M. Prognostic significance of host- and tumor-related factors in patients with gastric cancer. World J Surg. 2010;34:285–90.CrossRefPubMed Mohri Y, Tanaka K, Ohi M, Yokoe T, Miki C, Kusunoki M. Prognostic significance of host- and tumor-related factors in patients with gastric cancer. World J Surg. 2010;34:285–90.CrossRefPubMed
22.
go back to reference Jin H, Zhang G, Liu X, Liu X, Chen C, Yu H, et al. Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol. 2013;11:112.CrossRefPubMedCentralPubMed Jin H, Zhang G, Liu X, Liu X, Chen C, Yu H, et al. Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol. 2013;11:112.CrossRefPubMedCentralPubMed
23.
go back to reference Lee DY, Hong SW, Chang YG, Lee WY, Lee B. Clinical significance of preoperative inflammatory parameters in gastric cancer patients. J Gastric Cancer. 2013;13:111–6.CrossRefPubMedCentralPubMed Lee DY, Hong SW, Chang YG, Lee WY, Lee B. Clinical significance of preoperative inflammatory parameters in gastric cancer patients. J Gastric Cancer. 2013;13:111–6.CrossRefPubMedCentralPubMed
24.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
25.
go back to reference Dirican A, Ekinci N, Avci A, Akyol M, Alacacioglu A, Kucukzeybek Y, et al. The effects of hematological parameters and tumor-infiltrating lymphocytes on prognosis in patients with gastric cancer. Cancer Biomark. 2013;13:11–20.PubMed Dirican A, Ekinci N, Avci A, Akyol M, Alacacioglu A, Kucukzeybek Y, et al. The effects of hematological parameters and tumor-infiltrating lymphocytes on prognosis in patients with gastric cancer. Cancer Biomark. 2013;13:11–20.PubMed
26.
go back to reference Jeong JH, Lim SM, Yun JY, Rhee GW, Lim JY, Cho JY, et al. Comparison of two inflammation-based prognostic scores in patients with unresectable advanced gastric cancer. Oncology. 2012;83:292–9.CrossRefPubMed Jeong JH, Lim SM, Yun JY, Rhee GW, Lim JY, Cho JY, et al. Comparison of two inflammation-based prognostic scores in patients with unresectable advanced gastric cancer. Oncology. 2012;83:292–9.CrossRefPubMed
27.
go back to reference Wang DS, Ren C, Qiu MZ, Luo HY, Wang ZQ, Zhang DS, et al. Comparison of the prognostic value of various preoperative inflammation-based factors in patients with stage III gastric cancer. Tumour Biol. 2012;33:749–56.CrossRefPubMed Wang DS, Ren C, Qiu MZ, Luo HY, Wang ZQ, Zhang DS, et al. Comparison of the prognostic value of various preoperative inflammation-based factors in patients with stage III gastric cancer. Tumour Biol. 2012;33:749–56.CrossRefPubMed
28.
go back to reference Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88:218–30.CrossRefPubMed Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88:218–30.CrossRefPubMed
29.
go back to reference Satomi A, Murakami S, Ishida K, Mastuki M, Hashimoto T, Sonoda M. Significance of increased neutrophils in patients with advanced colorectal cancer. Acta Oncol. 1995;34:69–73.CrossRefPubMed Satomi A, Murakami S, Ishida K, Mastuki M, Hashimoto T, Sonoda M. Significance of increased neutrophils in patients with advanced colorectal cancer. Acta Oncol. 1995;34:69–73.CrossRefPubMed
30.
go back to reference Paramanathan A, Saxena A, Morris DL. A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol. 2014;23:31–9.CrossRefPubMed Paramanathan A, Saxena A, Morris DL. A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol. 2014;23:31–9.CrossRefPubMed
31.
go back to reference Zhang X, Zhang W, Feng LJ. Prognostic significance of neutrophil lymphocyte ratio in patients with gastric cancer: a meta-analysis. PLoS One. 2014;9:e111906.CrossRefPubMedCentralPubMed Zhang X, Zhang W, Feng LJ. Prognostic significance of neutrophil lymphocyte ratio in patients with gastric cancer: a meta-analysis. PLoS One. 2014;9:e111906.CrossRefPubMedCentralPubMed
32.
go back to reference Wu T, Li Y, Lu J, Qiao Q, Bao G, Wang N, et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer. Med Oncol. 2013;30:323.CrossRefPubMed Wu T, Li Y, Lu J, Qiao Q, Bao G, Wang N, et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer. Med Oncol. 2013;30:323.CrossRefPubMed
33.
go back to reference Kim DY, Cha ST, Ahn DH, Kang HY, Kwon CI, Ko KH, et al. STAT3 expression in gastric cancer indicates a poor prognosis. J Gastroenterol Hepatol. 2009;24:646–51.CrossRefPubMed Kim DY, Cha ST, Ahn DH, Kang HY, Kwon CI, Ko KH, et al. STAT3 expression in gastric cancer indicates a poor prognosis. J Gastroenterol Hepatol. 2009;24:646–51.CrossRefPubMed
34.
go back to reference Xiong H, Du W, Wang JL, Wang YC, Tang JT, Hong J, et al. Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. J Mol Med (Berl). 2012;90:1037–46.CrossRef Xiong H, Du W, Wang JL, Wang YC, Tang JT, Hong J, et al. Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. J Mol Med (Berl). 2012;90:1037–46.CrossRef
35.
go back to reference Dumitru CA, Lang S, Brandau S. Modulation of neutrophil granulocytes in the tumor microenvironment: mechanisms and consequences for tumor progression. Semin Cancer Biol. 2013;23:141–8.CrossRefPubMed Dumitru CA, Lang S, Brandau S. Modulation of neutrophil granulocytes in the tumor microenvironment: mechanisms and consequences for tumor progression. Semin Cancer Biol. 2013;23:141–8.CrossRefPubMed
36.
go back to reference Zhang R, Li F, Li H, Yu J, Ren X. The clinical significance of memory T cells and its subsets in gastric cancer. Clin Transl Oncol. 2014;16:257–65.CrossRefPubMed Zhang R, Li F, Li H, Yu J, Ren X. The clinical significance of memory T cells and its subsets in gastric cancer. Clin Transl Oncol. 2014;16:257–65.CrossRefPubMed
37.
go back to reference Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya T, et al. Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer. Ann Surg. 2002;236:184–90.CrossRefPubMedCentralPubMed Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya T, et al. Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer. Ann Surg. 2002;236:184–90.CrossRefPubMedCentralPubMed
38.
go back to reference Ramanathan ML, Roxburgh CS, Guthrie GJ, Orange C, Talwar D, Horgan PG, et al. Is perioperative systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer? Ann Surg Oncol. 2013;20:2172–9.CrossRefPubMed Ramanathan ML, Roxburgh CS, Guthrie GJ, Orange C, Talwar D, Horgan PG, et al. Is perioperative systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer? Ann Surg Oncol. 2013;20:2172–9.CrossRefPubMed
39.
go back to reference Schmidt SC, Hamann S, Langrehr JM, Hoflich C, Mittler J, Jacob D, et al. Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study. J Hepatobiliary Pancreat Surg. 2007;14:484–92.CrossRefPubMed Schmidt SC, Hamann S, Langrehr JM, Hoflich C, Mittler J, Jacob D, et al. Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study. J Hepatobiliary Pancreat Surg. 2007;14:484–92.CrossRefPubMed
40.
go back to reference Chiou SK, Hoa N, Hodges A, Ge L, Jadus MR. Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins. Apoptosis. 2014;19:1378–88.CrossRefPubMed Chiou SK, Hoa N, Hodges A, Ge L, Jadus MR. Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins. Apoptosis. 2014;19:1378–88.CrossRefPubMed
Metadata
Title
Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer
Authors
Jing Chen
Dongsheng Hong
You Zhai
Peng Shen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2015
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-015-0530-9

Other articles of this Issue 1/2015

World Journal of Surgical Oncology 1/2015 Go to the issue