The Diagnostic Roles of Cytokines in Hepatobiliary Cancers

Yavuz Savas Koca, Mahmut Bulbul, Ibrahim Barut, Yavuz Savas Koca, Mahmut Bulbul, Ibrahim Barut

Abstract

Objectives: The aim of this study was to investigate the role of several cytokines including IL-2, IL-6, IL-8, IL-10, and TNF-α in the diagnosis of HPB cancers.

Materials and methods: The prospective study was performed between October 2007 and September 2014. The study included 226 patients who were divided into 5 groups depending on their postoperative and histopathologic diagnosis: Control group included 30 healthy volunteers. Hepatocellular cancer (HCC) group included 24 patients diagnosed with HCC. Gallbladder cancer (GBC) group included 36 patients diagnosed with GBC. Cholangiocellular carcinoma group included 64 patients diagnosed with cholangiocellular carcinoma. Pancreatic cancer group included 72 patients diagnosed with pancreatic cancer. Serum levels of IL-2, IL-6, IL-8, IL-10, and TNF-α were measured using an enzyme-linked immunosorbent assay kit in accordance with the guidelines of the producer.

Results: Serum TNF-α concentration was significantly higher in the cholangiocellular carcinoma and pancreatic cancer groups compared to other groups. IL-6 and IL-10 were significantly increased in both the HCC and GBC groups, IL-2, IL-6, IL-10, and TNF-α in the cholangiocellular carcinoma group, and IL-2, IL-6, IL-8, and TNF-α in the pancreatic cancer group.

Conclusion: We suggest that cytokines can be used as useful markers in the diagnosis of HPB cancers.

Figures

Figure 1
Figure 1
Increased serum IL-2 concentration in the cholangiocellular carcinoma group (Group IV) (p = 0.018).
Figure 2
Figure 2
Increased serum IL-6 concentrations in the GBC and pancreatic cancer groups (Groups III and V) (p = 0.034 and p ≤ 0.001, resp.).
Figure 3
Figure 3
Significantly increased IL-8 concentration in the pancreatic group (p = 0.009).
Figure 4
Figure 4
Significantly increased serum IL-10 concentration in the HCC group (p = 0.003).
Figure 5
Figure 5
Significantly increased serum TNF-α concentration in the cholangiocellular carcinoma and pancreatic cancer groups (p = 0.007 and p = 0.044).

References

    1. Burak K., Angulo P., Pasha T. M., Egan K., Petz J., Lindor K. D. Incidence and Risk Factors for Cholangiocarcinoma in Primary Sclerosing Cholangitis. American Journal of Gastroenterology. 2004;99(3):523–526. doi: 10.1111/j.1572-0241.2004.04067.x.
    1. Abbas G., Lindor K. D. Cholangiocarcinoma in primary sclerosing cholangitis. Journal of Gastrointestinal Cancer. 2009;40(1-2):19–25. doi: 10.1007/s12029-009-9085-8.
    1. Roshani R., McCarthy F., Hagemann T. Inflammatory cytokines in human pancreatic cancer. Cancer Letters. 2014;345(2):157–163. doi: 10.1016/j.canlet.2013.07.014.
    1. Slingluff C. L., Jr. Immunology of cancer. In: Norton J. A., editor. Surgery; Basic Science and Clinical Evidence. New York, NY, USA: Springer; 2001.
    1. Cools N., Ponsaerts P., Van Tendeloo V. F. I., Berneman Z. N. Regulatory T cells and human disease. Clinical and Developmental Immunology. 2007;2007 doi: 10.1155/2007/89195.89195
    1. Wolf A. M., Wolf D., Steurer M., Gastl G., Gunsilius E., Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clinical Cancer Research. 2003;9(2):606–612.
    1. Barut I., Kaya S. The diagnostic value of C-reactive protein in bacterial translocation in experimental biliary obstruction. Advances in Clinical and Experimental Medicine. 2014;23(2):197–203. doi: 10.17219/acem/37054.
    1. Liyanage U. K., Moore T. T., Joo H.-G., et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. The Journal of Immunology. 2002;169(5):2756–2761. doi: 10.4049/jimmunol.169.5.2756.
    1. Ormandy L., Hillemann T., Wedemeyer H., Manns M. P., Greten T. F., Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Research. 2005;65(6):2457–2464. doi: 10.1158/0008-5472.CAN-04-3232.
    1. Grande C., Firvida J. L., Navas V., Casal J. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma. Anti-Cancer Drugs. 2006;17(1):1–12. doi: 10.1097/01.cad.0000182748.47353.51.
    1. Dempe S., Lavie M., Struyf S., et al. Antitumoral activity of parvovirus-mediated IL-2 and MCP-3/CCL7 delivery into human pancreatic cancer: Implication of leucocyte recruitment. Cancer Immunology, Immunotherapy. 2012;61(11):2113–2123. doi: 10.1007/s00262-012-1279-4.
    1. Xiao Z., Luo G., Liu C., et al. Molecular mechanism underlying lymphatic metastasis in pancreatic cancer. BioMed Research International. 2014;2014 doi: 10.1155/2014/925845.925845
    1. Heikkilä K., Ebrahim S., Lawlor D. A. Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. European Journal of Cancer. 2008;44(7):937–945. doi: 10.1016/j.ejca.2008.02.047.
    1. Hodge D. R., Hurt E. M., Farrar W. L. The role of IL-6 and STAT3 in inflammation and cancer. European Journal of Cancer. 2005;41(16):2502–2512. doi: 10.1016/j.ejca.2005.08.016.
    1. Song M., Kellum J. A. Interleukin-6. Critical Care Medicine. 2005;33(12):S463–S465. doi: 10.1097/01.CCM.0000186784.62662.A1.
    1. Aggarwal B. B., Shishodia S., Sandur S. K., Pandey M. K., Sethi G. Inflammation and cancer: how hot is the link? Biochemical Pharmacology. 2006;72(11):1605–1621. doi: 10.1016/j.bcp.2006.06.029.
    1. Holmer R., Goumas F. A., Waetzig G. H., Rose-John S., Kalthoff H. Interleukin-6: A villain in the drama of pancreatic cancer development and progression. Hepatobiliary & Pancreatic Diseases International. 2014;13(4):371–380. doi: 10.1016/S1499-3872(14)60259-9.
    1. Mott J. L., Gores G. J. Targeting IL-6 in cholangiocarcinoma therapy. American Journal of Gastroenterology. 2007;102(10):2171–2172. doi: 10.1111/j.1572-0241.2007.01394.x.
    1. Delitto D., Black B. S., Sorenson H. L., et al. The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival. BMC Cancer. 2015;15(1, article 783) doi: 10.1186/s12885-015-1820-x.
    1. Matsuo Y., Sawai H., Funahashi H., et al. Enhanced Angiogenesis Due to Inflammatory Cytokines from Pancreatic Cancer Cell Lines and Relation to Metastatic Potential. Pancreas. 2004;28(3):344–352. doi: 10.1097/00006676-200404000-00025.
    1. Hsia C.-Y., Huo T.-I., Chiang S.-Y., et al. Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma. European Journal of Surgical Oncology. 2007;33(2):208–212. doi: 10.1016/j.ejso.2006.10.036.
    1. Karakhanova S., Ryschich E., Mosl B., et al. Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma. British Journal of Cancer. 2015;112(6):1027–1036. doi: 10.1038/bjc.2015.72.
    1. Egberts J.-H., Cloosters V., Noack A., et al. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Research. 2008;68(5):1443–1450. doi: 10.1158/0008-5472.CAN-07-5704.
    1. Utaisincharoen P., Tangthawornchaikul N., Ubol S., Chaisuriya P., Sirisinha S. Tnf-α induces caspase 3 (CPP 32) dependent apoptosis in human cholangiocarcinoma cell line. Southeast Asian Journal of Tropical Medicine and Public Health. 2000;31(1):167–170.

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