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PMID: 23059742 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma.

British journal of cancer ·Vol. 107 ·No. 10 ·2012-11-06 ·Pages 1729-36

Kantola T, Klintrup K, Väyrynen JP, Vornanen J, Bloigu R, Karhu T, Herzig KH, Näpänkangas J, Mäkelä J, Karttunen TJ, Tuomisto A, Mäkinen MJ

Abstract

Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis. The serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil-lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls. CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls - including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) - yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu. CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.

MeSH Terms
Aged Chemokine CCL2/blood Colorectal Neoplasms/blood,metabolism,pathology Female Humans Inflammation/blood,pathology Interleukins/blood Male Neoplasm Staging Platelet-Derived Growth Factor/metabolism Prospective Studies
Chemicals
Chemokine CCL2 Interleukins Platelet-Derived Growth Factor
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Kantola T
Department of Pathology, University of Oulu, POB 5000, Oulu FI-90014, Finland.
Klintrup K
Väyrynen J P
Vornanen J
Bloigu R
Karhu T
Herzig K-H
Näpänkangas J
Mäkelä J
Karttunen T J
Tuomisto A
Mäkinen M J
References (48)
48 references, click to expand
  1. Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer.
    Clin Exp Metastasis. 2007;24(2):121-30 PMID: 17390111
  2. Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis.
    J Gastroenterol. 1994 Aug;29(4):423-9 PMID: 7951851
  3. Inflammation and prognosis in colorectal cancer.
    Eur J Cancer. 2005 Nov;41(17):2645-54 PMID: 16239109
  4. Tumor-associated Macrophages (TAM) and Inflammation in Colorectal Cancer.
    Cancer Microenviron. 2011 Aug;4(2):141-54 PMID: 21909876
  5. Differences in cytokine levels due to gender in colorectal cancer patients.
    Cytokine. 2010 Apr;50(1):91-3 PMID: 20116278
  6. Cancer-related inflammation.
    Nature. 2008 Jul 24;454(7203):436-44 PMID: 18650914
  7. Serum interleukin-6 levels in colorectal cancer patients--a summary of published results.
    Int J Colorectal Dis. 2010 Feb;25(2):135-40 PMID: 19898853
  8. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.
    Clin Chem. 2008 Dec;54(12):e11-79 PMID: 19042984
  9. Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I--an independent prognostic factor.
    Tumour Biol. 2005 Jul-Aug;26(4):186-94 PMID: 16006772
  10. Intratumoral macrophage counts correlate with tumor progression in colorectal cancer.
    J Surg Oncol. 2010 Sep 1;102(3):242-8 PMID: 20740582
  11. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues.
    Arch Pathol Lab Med. 2010 Jun;134(6):837-52 PMID: 20524862
  12. IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo.
    J Exp Med. 1993 Sep 1;178(3):1057-65 PMID: 8350046
  13. Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer.
    World J Gastroenterol. 2007 Oct 7;13(37):4996-5002 PMID: 17854143
  14. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
    Science. 2006 Sep 29;313(5795):1960-4 PMID: 17008531
  15. The role of chemokines in intestinal inflammation and cancer.
    Curr Opin Pharmacol. 2009 Dec;9(6):688-96 PMID: 19734090
  16. Harnessing the biology of IL-7 for therapeutic application.
    Nat Rev Immunol. 2011 May;11(5):330-42 PMID: 21508983
  17. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool.
    J Clin Invest. 2005 May;115(5):1177-87 PMID: 15841203
  18. Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer.
    Eur J Cancer. 2009 Aug;45(12):2138-45 PMID: 19409772
  19. Platelet-derived growth factor (subtype BB) is elevated in patients with colorectal carcinoma.
    Dis Colon Rectum. 2009 Jun;52(6):1166-71 PMID: 19581863
  20. Profile of monocyte chemoattractant protein-1 circulating levels in gastric cancer patients.
    Scand J Gastroenterol. 2002 Jul;37(7):830-3 PMID: 12190098
  21. The risk of colorectal cancer in ulcerative colitis: a meta-analysis.
    Gut. 2001 Apr;48(4):526-35 PMID: 11247898
  22. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer.
    Trends Mol Med. 2008 Mar;14(3):109-19 PMID: 18261959
  23. Th2-mediated anti-tumour immunity: friend or foe?
    Tissue Antigens. 2007 Jul;70(1):1-11 PMID: 17559575
  24. Immunologic messenger molecules: cytokines, interferons, and chemokines.
    J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S53-72 PMID: 19932918
  25. Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma.
    Cancer. 2004 Jan 15;100(2):270-8 PMID: 14716760
  26. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.
    Lancet. 2010 Nov 20;376(9754):1741-50 PMID: 20970847
  27. Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer.
    J Pathol. 1997 Jul;182(3):318-24 PMID: 9349235
  28. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study.
    Gastroenterology. 2007 Jul;133(1):48-56 PMID: 17631130
  29. Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer.
    J Transl Med. 2011 Sep 26;9:162 PMID: 21943235
  30. The risk of cancer in patients with Crohn's disease.
    Dis Colon Rectum. 2007 Jun;50(6):839-55 PMID: 17308939
  31. Serum monocyte chemoattractant protein-1 in patients with postoperative infectious complications from gastrointestinal surgery for cancer.
    World J Surg. 2004 Feb;28(2):130-6 PMID: 14708051
  32. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer.
    Future Oncol. 2010 Jan;6(1):149-63 PMID: 20021215
  33. Serum interleukin-6 levels reflect the disease status of colorectal cancer.
    J Surg Oncol. 2003 Aug;83(4):222-6 PMID: 12884234
  34. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer.
    Cancer Res. 1998 Aug 15;58(16):3491-4 PMID: 9721846
  35. Modulating T-cell homeostasis with IL-7: preclinical and clinical studies.
    J Intern Med. 2009 Aug;266(2):141-53 PMID: 19623690
  36. Inflammation and colon cancer.
    Gastroenterology. 2010 Jun;138(6):2101-2114.e5 PMID: 20420949
  37. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?
    Clin Chem. 2001 Apr;47(4):624-30 PMID: 11274010
  38. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.
    J Natl Cancer Inst. 2004 Oct 6;96(19):1420-5 PMID: 15467030
  39. The interleukin-8 pathway in cancer.
    Clin Cancer Res. 2008 Nov 1;14(21):6735-41 PMID: 18980965
  40. Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.
    Gut. 2006 Jan;55(1):54-61 PMID: 16085694
  41. Immune infiltration in human tumors: a prognostic factor that should not be ignored.
    Oncogene. 2010 Feb 25;29(8):1093-102 PMID: 19946335
  42. Interferon gamma-inducible protein 10 (IP-10), a member of the C-X-C chemokine family, is an inhibitor of angiogenesis.
    Biochem Biophys Res Commun. 1995 May 5;210(1):51-7 PMID: 7537965
  43. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.
    Lancet. 2011 Dec 17;378(9809):2081-7 PMID: 22036019
  44. Polarization of cytokine profile from Th1 into Th2 along colorectal adenoma-carcinoma sequence: implications for the biotherapeutic target?
    Inflamm Allergy Drug Targets. 2008 Jun;7(2):94-7 PMID: 18691138
  45. Disregulation in TH1 and TH2 subsets of CD4+ T cells in peripheral blood of colorectal cancer patients and involvement in cancer establishment and progression.
    Cancer Immunol Immunother. 1996 Jan;42(1):1-8 PMID: 8625361
  46. Differentiation-dependent expression and mitogenic action of interleukin-6 in human colon carcinoma cells: relevance for tumour progression.
    Eur J Cancer. 2005 Oct;41(15):2347-54 PMID: 16176872
  47. PDGF and vessel maturation.
    Recent Results Cancer Res. 2010;180:103-14 PMID: 20033380
  48. Reduced beta-catenin and peroxisome proliferator-activated receptor-gamma expression levels are associated with colorectal cancer metastatic progression: correlation with tumor-associated macrophages, cyclooxygenase 2, and patient outcome.
    Hum Pathol. 2009 May;40(5):714-25 PMID: 19121846
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
Published
2012-11-06
Epub
2012-00-11
Pages
1729-36
Language
English
Region
England
NLM ID
0370635
PMCID
PMC3493870
Subset
IM
Corrections
CommentIn
CommentIn
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