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Evaluation of Serum Interleukin-17 (IL-17) Levels as a Diagnostic Marker in Pancreatic Adenocarcinoma

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Abstract

Background

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression. The role of interleukin (IL-17) in cancer is currently under debate. This study was conducted to investigate the serum levels of IL-17 in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters.

Material and Methods

Thirty-five patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum IL-17 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 35 healthy controls were included in the analysis.

Results

The median age at diagnosis was 61 years, range 38–84 years; 21 (60 %) patients were men. The tumor was located in the head of pancreas in 24 (69 %) patients. The most common metastatic site was liver in 20 patients with metastasis (n = 18, 90 %). The median follow-up time was 24.0 weeks (range 1.0–191.0 weeks). At the end of the observation period, 12 (34 %) patients experienced disease progression and 23 patients (66 %) were dead. Forty-four percent of 18 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. Median progression-free survival and overall survival of the whole group were 13.7 ± 2.3 weeks [95 % confidence interval (CI) = 9–18 weeks] and 48.0 ± 12.8 weeks (95 % CI = 23–73 weeks), respectively. The baseline serum IL-17 levels were significantly higher in patients with PA than in the control group (p = 0.001). Moreover, serum IL-17 levels were significantly higher in the patients with large pathologic tumor status and low albumin levels (p = 0.04 and p = 0.03, respectively). However, serum IL-17 assays had no prognostic roles on outcome.

Conclusion

Although serum levels of IL-17 assays were found to be diagnostic value, no predictive and prognostic value was determined in PA patients.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5.

    Article  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69.

    Article  PubMed  Google Scholar 

  3. Zhang J, Dhakal I, Ning B, Kesteloot H. Patterns and trends of pancreatic cancer mortality rates in Arkansas, 1969–2002: a comparison with the US population. Eur J Cancer Prev. 2008;17:18.

    Article  PubMed  Google Scholar 

  4. Yao Z, Franslow WC, Seldin MF, Rousseau A-M, Painter SL, Comeau MR, et al. Herpes virus saimiri encodes a new cytokine IL-17 which binds to novel cytokine receptor. Immunity. 1995;3:811–21.

    Article  CAS  PubMed  Google Scholar 

  5. Shin HC, Benbernou N, Esnault S, Guenounou M. Expression of IL-17 in human memory CD45RO+ T lymphocytes and its regulation by protein kinase A pathway. Cytokine. 1999;11:257–66.

    Article  CAS  PubMed  Google Scholar 

  6. Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–11.

    Article  CAS  PubMed  Google Scholar 

  7. Schwartz S, Beaulieu JF, Ruemmele FM. Interleukin-17 is a potent immuno-modulator and regulator of normal human intestinal epithelial cell growth. Biochem Biophys Res Commun. 2005;337:505–9.

    Article  CAS  PubMed  Google Scholar 

  8. Gnerlich JL, Mitchem JB, Weir JS, Sankpal NV, Kashiwagi H, Belt BA, et al. Induction of Th17 cells in the tumor microenvironment improves survival in a murine model of pancreatic cancer. J Immunol. 2010;185(7):4063–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Andoh A, Shimada M, Bamba S, Okuno T, Araki Y, Fujiyama Y, et al. Extracellular signal-regulated kinases 1 and 2 participate in interleukin-17 plus tumor necrosis factor-alpha-induced stabilization of interleukin-6 mRNA in human pancreatic myofibroblasts. Biochim Biophys Acta. 2002;1591(1–3):69–74.

    Article  CAS  PubMed  Google Scholar 

  10. Bos PD, Rudensky AY. Treg cells in cancer: a case of multiple personality disorder. Sci Transl Med. 2012;4(164):164fs144.

    Article  Google Scholar 

  11. Kato T, Furumoto H, Ogura T, Onishi Y, Irahara M, Yamano S, et al. Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun. 2001;282:735–8.

    Article  CAS  PubMed  Google Scholar 

  12. Meng XY, Zhou CH, Ma J, Jiang C, Ji P. Expression of interleukin-17 and its clinical significance in gastric cancer patients. Med Oncol. 2012;29(5):3024–8.

    Article  CAS  PubMed  Google Scholar 

  13. Wu X, Zeng Z, Xu L, Yu J, Cao Q, Chen M, et al. Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis. Tumor Biol. 2014;35(6):5347–56.

    Article  CAS  Google Scholar 

  14. Xu C, Hao K, Yu L, Zhang X. Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer. Biomarkers. 2014;19(4):287–90.

    Article  CAS  PubMed  Google Scholar 

  15. Xu C, Yu L, Zhan P, Zhang Y. Elevated pleural effusion IL-17 is a diagnostic marker and outcome predictor in lung cancer patients. Eur J Med Res. 2014;19:23.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Baharlou R, Ahmadi Vasmehjani A, Dehghani A, Ghobadifar MA, Khoubyari M. Reduced interleukin17 and transforming growth factor beta levels in peripheral blood as indicators for following the course of bladder cancer. Immune Netw. 2014;14(3):156–63.

    Article  PubMed Central  PubMed  Google Scholar 

  17. He S, Fei M, Wu Y, Zheng D, Wan D, Wang L, et al. Distribution and clinical significance of Th17 cells in the tumor microenvironment and peripheral blood of pancreatic cancer patients. Int J Mol Sci. 2011;12(11):7424–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Miura T, Mitsunaga S, Ikeda M, Shimizu S, Ohno I, Takahashi H, et al. Characterization of patients with advanced pancreatic cancer and high serum interleukin-6 levels. Pancreas. 2015;44(5):756–63.

    Article  CAS  PubMed  Google Scholar 

  19. Poutou J, Bunuales M, Gonzalez-Aparicio M, Garcia-Aragoncillo E, Quetglas JI, Casado R, et al. Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model. Gene Ther 2015. doi: 10.1038/gt.2015.45.

  20. Komura T, Sakai Y, Harada K, Kawaguchi K, Takabatake H, Kitagawa H, et al. Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact. Cancer Sci. 2015;106(6):672–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Leach SD. Interleukin interrupted: a new strategy for the treatment of pancreatic cancer. J Exp Med. 2015;212(3):284.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Wu HH, Hwang-Verslues WW, Lee WH, Huang CK, Wei PC, Chen CL, et al. Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines. J Exp Med. 2015;212(3):333–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. McCawley LJ, Matrisian LM. Tumor progression: defining the soil round the tumor seed. Curr Biol. 2001;11(1):R25–7.

    Article  CAS  PubMed  Google Scholar 

  25. Farrow B, Evers BM. Inflammation and the development of pancreatic cancer. Surg Oncol. 2002;10(4):153–69.

    Article  PubMed  Google Scholar 

  26. Ben-Baruch A. Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol. 2006;16(1):38–52.

    Article  CAS  PubMed  Google Scholar 

  27. Lin Y, Xu J, Su H, Zhong W, Yuan Y, Yu Z, et al. Interleukin-17 is a favorable prognostic marker for colorectal cancer. Clin Transl Oncol. 2015;17(1):50–6.

    Article  CAS  PubMed  Google Scholar 

  28. McAllister F, Bailey JM, Alsina J, Nirschl CJ, Sharma R, Fan H, et al. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer Cell. 2014;25(5):621–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Gaspari AA, Tyring S. New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors. Dermatol Ther. 2015;28(4):179–93.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Varas A, Valencia J, Lavocat F, Martínez VG, Thiam NN, Hidalgo L, et al. Blockade of bone morphogenetic protein signaling potentiates the pro-inflammatory phenotype induced by interleukin-17 and tumor necrosis factor-α combination in rheumatoid synoviocytes. Arthritis Res Ther. 2015;17:192.

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey

    Senem Karabulut, Leyla Kılıc & Nuri Faruk Aykan

  2. Department of Medical Oncology, Istanbul Education and Research Hospital, Istanbul, Turkey

    Çiğdem Usul Afsar

  3. Clinic of General Surgery, Istanbul Bakırköy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey

    Mehmet Karabulut, Halil Alış & Murat Çikot

  4. Department of Basic Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey

    Ceren Tilgen Yasasever

Authors
  1. Senem Karabulut
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  2. Çiğdem Usul Afsar
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  3. Mehmet Karabulut
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  4. Halil Alış
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Correspondence to Çiğdem Usul Afsar.

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Karabulut, S., Afsar, Ç.U., Karabulut, M. et al. Evaluation of Serum Interleukin-17 (IL-17) Levels as a Diagnostic Marker in Pancreatic Adenocarcinoma. J Gastrointest Canc 47, 47–54 (2016). https://doi.org/10.1007/s12029-015-9787-z

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  • DOI: https://doi.org/10.1007/s12029-015-9787-z

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