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Erschienen in: Journal of Gastrointestinal Cancer 1/2016

01.03.2016 | Original Research

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

verfasst von: Senem Karabulut, Çiğdem Usul Afsar, Mehmet Karabulut, Halil Alış, Leyla Kılıc, Murat Çikot, Ceren Tilgen Yasasever, Nuri Faruk Aykan

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1/2016

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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.
Literatur
1.
2.
3.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–11.CrossRefPubMed Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–11.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
8.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat Bos PD, Rudensky AY. Treg cells in cancer: a case of multiple personality disorder. Sci Transl Med. 2012;4(164):164fs144.CrossRef Bos PD, Rudensky AY. Treg cells in cancer: a case of multiple personality disorder. Sci Transl Med. 2012;4(164):164fs144.CrossRef
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRef 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.CrossRef
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
16.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
19.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
22.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
23.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
24.
Zurück zum Zitat McCawley LJ, Matrisian LM. Tumor progression: defining the soil round the tumor seed. Curr Biol. 2001;11(1):R25–7.CrossRefPubMed McCawley LJ, Matrisian LM. Tumor progression: defining the soil round the tumor seed. Curr Biol. 2001;11(1):R25–7.CrossRefPubMed
25.
Zurück zum Zitat Farrow B, Evers BM. Inflammation and the development of pancreatic cancer. Surg Oncol. 2002;10(4):153–69.CrossRefPubMed Farrow B, Evers BM. Inflammation and the development of pancreatic cancer. Surg Oncol. 2002;10(4):153–69.CrossRefPubMed
26.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
27.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
29.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
30.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
Metadaten
Titel
Evaluation of Serum Interleukin-17 (IL-17) Levels as a Diagnostic Marker in Pancreatic Adenocarcinoma
verfasst von
Senem Karabulut
Çiğdem Usul Afsar
Mehmet Karabulut
Halil Alış
Leyla Kılıc
Murat Çikot
Ceren Tilgen Yasasever
Nuri Faruk Aykan
Publikationsdatum
01.03.2016
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1/2016
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-015-9787-z

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