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PMID: 22442706 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

PloS one ·Vol. 7 ·No. 3 ·2012-00-00 ·Pages e33655

Zhao JJ, Pan K, Wang W, Chen JG, Wu YH, Lv L, Li JJ, Chen YB, Wang DD, Pan QZ, Li XD, Xia JC

Abstract

Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.

MeSH Terms
Adenocarcinoma/metabolism,mortality,pathology,surgery Adult Aged Disease-Free Survival Female Follow-Up Studies Fucosyltransferases/biosynthesis Humans Lewis X Antigen/biosynthesis Male Middle Aged Neoplasm Proteins/biosynthesis Neutrophil Infiltration Neutrophils/metabolism,pathology Stomach Neoplasms/metabolism,mortality,pathology,surgery Survival Rate
Chemicals
Lewis X Antigen Neoplasm Proteins FUT4 protein, human Fucosyltransferases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zhao Jing-jing
State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
Pan Ke
Wang Wei
Chen Ju-gao
Wu Yan-heng
Lv Lin
Li Jian-jun
Chen Yi-bing
Wang Dan-dan
Pan Qiu-zhong
Li Xiao-dong
Xia Jian-chuan
References (29)
29 references, click to expand
  1. Neutrophils and immunity: challenges and opportunities.
    Nat Rev Immunol. 2006 Mar;6(3):173-82 PMID: 16498448
  2. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer.
    Oncology. 2007;73(3-4):215-20 PMID: 18424885
  3. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.
    Nat Cell Biol. 2000 Oct;2(10):737-44 PMID: 11025665
  4. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
    Science. 2006 Sep 29;313(5795):1960-4 PMID: 17008531
  5. Neutrophil granulocytes promote the migratory activity of MDA-MB-468 human breast carcinoma cells via ICAM-1.
    Exp Cell Res. 2010 Jan 1;316(1):138-48 PMID: 19747913
  6. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma.
    J Hepatol. 2011 May;54(5):948-55 PMID: 21145847
  7. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer.
    J Surg Oncol. 2011 Oct;104(5):504-10 PMID: 21618251
  8. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy.
    Mod Pathol. 2002 Aug;15(8):831-7 PMID: 12181268
  9. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.
    Cancer. 2000 Aug 1;89(3):523-33 PMID: 10931451
  10. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis.
    Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12493-8 PMID: 16891410
  11. Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner.
    Clin Immunol. 2010 Mar;134(3):277-88 PMID: 19900843
  12. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2640-5 PMID: 18268320
  13. Cancer: Inflaming metastasis.
    Nature. 2009 Jan 1;457(7225):36-7 PMID: 19122629
  14. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial.
    J Clin Oncol. 2007 Apr 20;25(12):1562-9 PMID: 17443000
  15. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent.
    Cancer Cell. 2005 May;7(5):411-23 PMID: 15894262
  16. Neutrophils and angiogenesis: potential initiators of the angiogenic cascade.
    Chem Immunol Allergy. 2003;83:167-81 PMID: 12947984
  17. CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer.
    Cancer Res. 2005 Mar 1;65(5):2018-25 PMID: 15753402
  18. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
    Cell. 2006 Jan 27;124(2):263-6 PMID: 16439202
  19. The prevalence of Th17 cells in patients with gastric cancer.
    Biochem Biophys Res Commun. 2008 Sep 26;374(3):533-7 PMID: 18655770
  20. The accumulation and prognosis value of tumor infiltrating IL-17 producing cells in esophageal squamous cell carcinoma.
    PLoS One. 2011 Mar 31;6(3):e18219 PMID: 21483813
  21. Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis.
    Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20262-7 PMID: 18077379
  22. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection.
    J Hepatol. 2011 Mar;54(3):497-505 PMID: 21112656
  23. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma.
    J Clin Oncol. 2009 Oct 1;27(28):4709-17 PMID: 19720929
  24. Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients.
    Int J Biol Sci. 2011 Jan 11;7(1):53-60 PMID: 21234303
  25. Inflammation and cancer.
    Nature. 2002 Dec 19-26;420(6917):860-7 PMID: 12490959
  26. High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer.
    Gastric Cancer. 2010 Aug;13(3):170-6 PMID: 20820986
  27. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression.
    Cancer Res. 2005 Oct 1;65(19):8896-904 PMID: 16204061
  28. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells.
    Hepatology. 2010 Jan;51(1):154-64 PMID: 19902483
  29. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model.
    Br J Cancer. 2005 Aug 8;93(3):273-8 PMID: 16052222
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
Published
2012-00-00
Epub
2012-00-19
Pages
e33655
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3307751
Subset
IM
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