Skip to main content

Advertisement

SpringerLink
Log in

The combined use of serum neurotensin and IL-8 as screening markers for colorectal cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

This pilot study aimed to determine the feasibility of serum neurotensin/IL-8 values being used as a screening tool for colorectal cancer. Fifty-six patients and 15 healthy controls were assigned to seven groups according to their disease entity based on theater records and histology report. Blood samples for neurotensin and IL-8 were measured using an enzyme-linked immunosorbent assay. There were no differences in the clinical and biochemical parameters of patients and controls. Group (p = 0.003) and age (p = 0.059, marginally significant) were independent predictors of neurotensin plasma values. Neurotensin (p = 0.004) and IL-8 (p = 0.029) differed between healthy and colorectal cancer patients. Neurotensin values differentiate the control group from all remaining groups. The value of plasma neurotensin ≤54.47 pg/ml at enrollment selected by receiver operating characteristic (ROC) curves demonstrated a sensitivity of 77 %, specificity of 90 %, and an estimate of area under ROC curve (accuracy) of 85 % in predicting colorectal cancer. At enrollment, the value of plasma IL-8 ≥8.83 pg/ml had a sensitivity of 85 %, specificity 80 %, and an estimate of area under ROC curve (accuracy) of 81 % in predicting colorectal cancer. IL-8 should be used complementary to neurotensin due to its lower specificity. None of the colorectal cancer patients displayed a combination of high neurotensin and low IL-8 values (beyond cutoffs). It seems that a blood neurotensin/IL-8 system may be used as a screening tool for colorectal cancer, but much has to be done before it is validated in larger-scale prospective studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130–60.

    Article  PubMed  Google Scholar 

  2. U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:627–37.

    Article  Google Scholar 

  3. Knudsen AB, Hur C, Gazelle GS, Schrag D, McFarland EG, Kuntz KM. Rescreening of persons with a negative colonoscopy result: results from a microsimulation model. Ann Intern Med. 2012;157:611–20.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Hassan C, Giorgi Rossi P, Camilloni L, Rex DK, Jimenez-Cendales B, Ferroni E, et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther. 2012;36:929–40.

    Article  CAS  PubMed  Google Scholar 

  5. National Comprehensive Cancer Network (2013) Colorectal cancer screening (version 2.2013). http://www.nccn.org/professionals/physician_gls/gl_steering_committee.asp. Accessed 16 Dec 2013

  6. Carraway RE, Plona AM. Involvement of neurotensin in cancer growth: evidence, mechanisms and development of diagnostic tools. Peptides. 2006;27:2445–60.

    Article  CAS  PubMed  Google Scholar 

  7. Bugni JM, Rabadi LA, Jubbal K, Karagiannides I, Lawson G, Pothoulakis C. The neurotensin receptor-1 promotes tumor development in a sporadic but not an inflammation-associated mouse model of colon cancer. Int J Cancer. 2012;130:1798–805.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Vincent JP. Neurotensin receptors: binding properties, transduction pathways, and structure. Cell Mol Neurobiol. 1995;15:501–12.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao D, Zhan Y, Koon HW, Zeng H, Keates S, Moyer MP, et al. Metalloproteinase-dependent transforming growth factor-alpha release mediates neurotensin-stimulated MAP kinase activation in human colonic epithelial cells. J Biol Chem. 2004;279:43547–54.

    Article  CAS  PubMed  Google Scholar 

  10. Ehlers RA, Zhang Y, Hellmich MR, Evers BM. Neurotensin-mediated activation of MAPK pathways and AP-1 binding in the human pancreatic cancer cell line, MIA PaCa-2. Biochem Biophys Res Commun. 2000;269:704–8.

    Article  CAS  PubMed  Google Scholar 

  11. Ehlers 2nd RA, Bonnor RM, Wang X, Hellmich MR, Evers BM. Signal transduction mechanisms in neurotensin-mediated cellular regulation. Surgery. 1998;124:239–46. discussion 246–237.

    Article  PubMed  Google Scholar 

  12. Zhao D, Keates AC, Kuhnt-Moore S, Moyer MP, Kelly CP, Pothoulakis C. Signal transduction pathways mediating neurotensin-stimulated interleukin-8 expression in human colonocytes. J Biol Chem. 2001;276:44464–71.

    Article  CAS  PubMed  Google Scholar 

  13. Bossard C, Souaze F, Jarry A, Bezieau S, Mosnier JF, Forgez P, et al. Over-expression of neurotensin high-affinity receptor 1 (NTS1) in relation with its ligand neurotensin (NT) and nuclear beta-catenin in inflammatory bowel disease-related oncogenesis. Peptides. 2007;28:2030–5.

    Article  CAS  PubMed  Google Scholar 

  14. Maoret JJ, Anini Y, Rouyer-Fessard C, Gully D, Laburthe M. Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice. Int J Cancer. 1999;80:448–54.

    Article  CAS  PubMed  Google Scholar 

  15. Gui X, Guzman G, Dobner PR, Kadkol SS. Increased neurotensin receptor-1 expression during progression of colonic adenocarcinoma. Peptides. 2008;29:1609–15.

    Article  CAS  PubMed  Google Scholar 

  16. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996;348:1467–71.

    Article  CAS  PubMed  Google Scholar 

  17. Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, et al. Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Gastroenterology. 2000;119:1219–27.

    Article  CAS  PubMed  Google Scholar 

  18. Müller KM, Tveteraas IH, Aasrum M, Odegard J, Dawood M, Dajani O, et al. Role of protein kinase c and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells. BMC Cancer. 2011;11:421.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Potten CS, Booth C, Pritchard DM. The intestinal epithelial stem cell: the mucosal governor. Int J Exp Pathol. 1997;78:219–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Souaze F, Viardot-Foucault V, Roullet N, Toy-Miou-Leong M, Gompel A, Bruyneel E, et al. Neurotensin receptor 1 gene activation by the TCF/beta-catenin pathway is an early event in human colonic adenomas. Carcinogenesis. 2006;27:708–16.

    Article  CAS  PubMed  Google Scholar 

  21. van Eeden SF, Terashima T. Interleukin 8 (IL-8) and the release of leukocytes from the bone marrow. Leuk Lymphoma. 2000;37:259–71.

    PubMed  Google Scholar 

  22. Wang X, Wang Q, Ives KL, Evers BM. Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells. Clin Cancer Res. 2006;12:5346–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Gully D, Labeeuw B, Boigegrain R, Oury-Donat F, Bachy A, Poncelet M, et al. Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther. 1997;280:802–12.

    CAS  PubMed  Google Scholar 

  24. Mazella J, Botto JM, Guillemare E, Coppola T, Sarret P, Vincent JP. Structure, functional expression, and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain. J Neurosci. 1996;16:5613–20.

    CAS  PubMed  Google Scholar 

  25. Mazella J, Vincent JP. Functional roles of the NTS2 and NTS3 receptors. Peptides. 2006;27:2469–75.

    Article  CAS  PubMed  Google Scholar 

  26. Leeman SE, Carraway RE. Neurotensin: discovery, isolation, characterization, synthesis and possible physiological roles. Ann N Y Acad Sci. 1982;400:1–16.

    Article  CAS  PubMed  Google Scholar 

  27. Kitabgi P. Inactivation of neurotensin and neuromedin N by Zn metallopeptidases. Peptides. 2006;27:2515–22.

    Article  CAS  PubMed  Google Scholar 

  28. Wolf AM, Wender RC, Etzioni RB, Thompson IM, D’Amico AV, Volk RJ, et al. American Cancer Society guideline for the early detection of prostate cancer: update. CA Cancer J Clin. 2010;60:70–98.

    Article  PubMed  Google Scholar 

  29. Martin S, Navarro V, Vincent JP, Mazella J. Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line. Gastroenterology. 2002;123:1135–43.

    Article  CAS  PubMed  Google Scholar 

  30. Mantuano E, Santi S, Filippi C, Manca-Rizza G, Paoletti S, Consani C, et al. Simvastatin and fluvastatin reduce interleukin-6 and interleukin-8 lipopolysaccharide (LPS) stimulated production by isolated human monocytes from chronic kidney disease patients. Biomed Pharmacother. 2007;61:360–5.

    Article  CAS  PubMed  Google Scholar 

  31. Malicki S, Winiarski M, Matlok M, Kostarczyk W, Guzdek A, Konturek PC. Il-6 and il-8 responses of colorectal cancer in vivo and in vitro cancer cells subjected to simvastatin. J Physiol Pharmacol. 2009;60:141–6.

    CAS  PubMed  Google Scholar 

  32. Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases il-6 and il-8 production in epithelial cells. J Dent Res. 2006;85:520–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present work was funded by the Department of Biological Chemistry, University of Athens Medical School, Athens, Greece, annual budget 2012.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Second Department of Surgery and Surgical Oncology Unit, Red Cross Hospital, 1, Athanasaki Street, Ampelokipi, 11526, Athens, Greece

    George Sgourakis, Christos Kontovounisios, Georgia Dedemadi & Constantine Karaliotas

  2. Department of Biological Chemistry, University of Athens Medical School, 75, Mikras Asias Street, Goudi, 11527, Athens, Greece

    Aggeliki Papapanagiotou, Michalis V. Karamouzis & Athanasios G. Papavassiliou

  3. Department of Gastroenterology, Red Cross Hospital, Athens, Greece

    Constantine Goumas

Authors
  1. George Sgourakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aggeliki Papapanagiotou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christos Kontovounisios
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michalis V. Karamouzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Georgia Dedemadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Constantine Goumas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Constantine Karaliotas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Athanasios G. Papavassiliou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Athanasios G. Papavassiliou.

Additional information

George Sgourakis and Aggeliki Papapanagiotou contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sgourakis, G., Papapanagiotou, A., Kontovounisios, C. et al. The combined use of serum neurotensin and IL-8 as screening markers for colorectal cancer. Tumor Biol. 35, 5993–6002 (2014). https://doi.org/10.1007/s13277-014-1794-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1794-3

Keywords

Search

Navigation