Yener AYDIN, İbrahim KAPLAN, Yusuf BİLEN, Çağlar BULUT, Fatma GENÇ, Atila TÜRKYILMAZ, Atila EROĞLU

Plasma levels of IL-6 and TNF-a in patients with esophageal cancer

Cytokines are multifunctional polypeptides synthesized in various cell types. Interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) are cytokines that have important roles in cancer pathogenesis. In this study, we investigated the plasma levels of IL-6 and TNF-a in patients with esophageal cancer. Materials and methods: Forty-three esophageal cancer patients (24 females and 19 males) who were newly diagnosed and had not yet undergone operation participated in the study. The patients' average age was 61.03 ± 12.4 years. The control group, on the other hand, comprised 43 healthy individuals (22 males and 21 females) with an average age of 56 ± 11.3. Forty-one (95.3%) of the patients had symptoms of dysphagia. The second leading symptom was weight loss, experienced by 32 (74.4%) of the patients. The cancer of 5 (11.6%) of the patients advanced in stage and had distant metastases (2 involving the lung and 3 involving the liver) at presentation. TNF-a (TNF-a-EASIA Kit, DIAsource) and IL-6 (IL-6-EASIA Kit, DIAsource) were studied using the enzyme-linked immunosorbent assay (ELISA) method. Results: The measured TNF-a plasma levels of the patients and the control group were 12.35 ± 9.69 and 4.62 ± 3.06 pg/mL, respectively (P < 0.0001). The average TNF-a plasma levels of the patients with and without weight loss were 14.95 ± 9.96 and 4.77 ± 3.12 pg/mL, respectively (P = 0.044). The average IL-6 plasma level of the esophageal cancer patients was 60.30 ± 53.15 pg/mL, and the average IL-6 plasma level of the control group was 6.00 ± 3.26 pg/mL (P < 0.0001). The average IL-6 levels of the patients with and without weight loss were 65.22 ± 43.27 and 12.37 ± 6.80 pg/mL, respectively (P < 0.0001). There was no statistically significant difference in the IL-6 and TNF-a plasma levels of the patients with and without distant metastasis. Conclusion: The results show that IL-6 and TNF-a plasma levels may be utilized as tumor markers for the diagnosis of esophageal cancer. However, to definitely conclude this, we need further extensive studies.

Anahtar Kelimeler:

Key words: Esophageal cancer, IL-6, TNF-a

Plasma levels of IL-6 and TNF-a in patients with esophageal cancer

Keywords:

Key words: Esophageal cancer, IL-6, TNF-a,

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Türkyılmaz A, Eroğlu A, Aydın Y, Yılmaz Ö, Karaoğlanoğlu N. Survival in esophageal cancer patients with hematogenous distant organ metastases. Turk J Med Sci 2009; 39: 415-21. 2. Millikan KW, Silverstein J, Hart V, Blair K, Bines S, Roberts J et al. A 15-year review of esophagectomy for carcinoma of the esophagus and cardia. Arch Surg 1995; 130: 617-24. 3. Türkyılmaz A, Eroğlu A, Aydın Y, Yılmaz Ö, Karaoğlanoğlu N. Th e relationship of serum CEA and CA 19-9 levels to liver metastasis and pancreatic invasion in esophageal cancer. Turk J Med Sci 2009; 39: 895-9. 4.
Karadağ R, Koca C, Totan Y, Yağcı R, Aydın M, Karadağ AS et
al. Comparison of serum levels of IL-6, IL-8, TNF-α, C reactive
protein and heat shock protein 70 in patients with active or
inactive Behçet’s disease. Turk J Med Sci 2010; 40: 57-62.
Gülseken KH, Köksal İT, Özdem S, Saka O. Prediction of prostate cancer using decision tree algorithm. Turk J Med Sci 2010; 40: 681-6. 6. Sacu D, Bildik A. Levels of interleukin 6 and tumor necrosis factor-α in serum from fi brosarcoma induced rats. Kafk as Univ Vet Med Journal 2009; 15: 681-6.
Koszałka P, Szmit E, Myśliwski A, Bigda J. Anti-tumor action of tumor necrosis factor against Bomirski Ab melanoma in hamsters. Arch Immunol Th er Exp 2007; 55: 267-79.
Ebrahimi B, Tucker SL, Li D, Abbruzzese JL, Kurzrock R. Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis. Cancer 2004; 101: 2727-36. 9. Kemik Ö, Sarbay Kemik A, Dülger AC, Hasırcı İ, Daştan E, Bartın MK et al. Th e serum levels of interleukin-6 in colon cancer patients with liver metastasis. Van Med J 2010; 17: 42-5.
Ben-Baruch A. Host microenvironment in breast cancer development: infl ammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor microenvironment interactions. Breast Cancer Res 2003; 5: 31-6.
Van der Zee AGJ, de Cuyper EMJ, Limburg PC, de Bruijn HWA, Hollema H, Bijzet J et al. Higher levels of interleukin-6 in cystic fl uids from patients with malignant versus benign ovarian tumors correlate with decreased hemoglobin levels and increased platelet counts. Cancer 1995; 75: 1004-9.
Watson JM, Sensintaff ar JL, Berek JS, Martinez-Maza O. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990; 50: 6959-65.
Obata NH, Tamakoshi K, Shibata K, Kikkawa F, Tomoda Y. Eff ects of interleukin-6 on in vitro cell attachment, migration and invasion of human carcinoma. Anticancer Res 1997; 17: 337-42.
Nash MA, Fernandina G, Gordinier M, Loercher A, Freedman RS. Th e role of cytokines in both the normal and malignant ovary. Endocr Rel Cancer 1999; 6: 93-107.
Ashizawa T, Okada R, Suzuki Y, Takagi M, Yamazaki T, Sumi T et al. Study of interleukin-6 in the spread of colorectal cancer: the diagnostic signifi cance of IL-6. Acta Med Okayama 2006; 60: 325-30.
Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients--a summary of published results. Int J Colorectal Dis 2010; 25: 135-40.
De Vita F, Romano C, Orditura M, Galizia G, Martinelli E, Lieto E et al. Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator. J Interferon Cytokine Res 2001; 21: 45-52.
Seymour JF, Talpaz M, Cabanillas F, Wetzler M, Kurzrock R. Serum interleukin-6 levels correlate with prognosis in diff use large cell lymphoma. J Clin Oncol 1995; 13: 575-82.
Kurzrock R. Th e role of cytokines in cancer-related fatigue. Cancer 2001; 92: 1684-8.
Okada S, Okusaka T, Ishii H, Kyogoku A, Yoshimori M, Kajimura N et al. Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol 1998; 28: 12-5.
Falconer JS, Fearon KC, Plester CE, Ross JA, Carter DC. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 1994; 219: 325-31.
Nakagoe T, Tsuji T, Sawai T, Tanaka K, Hidaka S, Shibasaki S et al. Increased serum levels of interleukin-6 in malnourished patients with colorectal cancer. Cancer Letters 2003; 202: 109-15.
Konukoğlu D, Turhan SM. Molecular basis of angiogenesis mechanisms and tumor angiogenesis. Cerrahpaşa J Med 2005; 36: 42-8.
Kelle İ. Biotoxins in cancer therapy. Dicle Tıp Dergisi 2007; 34: 226-32.
Şenel S, Kılıçkap S. Anti-tumor necrosis factor therapy and cancer. Cumhuriyet Med J 2010; 32: 132-6.
Kulbe H, Th ompson R, Wilson JL, Robinson S, Hagemann T, Fatah R et al. Th e infl ammatory cytokine tumor necrosis factor-α generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Res 2007; 67: 585-92.
Kulbe H, Hagermann T, Szlosarek PW, Balkwill FR, Wilson JL. Th e infl ammatory cytokine TNF-α upregulates chemokine receptor expression on ovarian cancer cells. Cancer Res 2005; 65: 10355-62.
Shouda T, Hiraoka K, Komiya S, Hamada T, Zenmyo M, Iwasaki H et al. Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells. Cancer Lett 2004; 231: 176-84.
Grimm EA, Smid CM, Lee JJ, Tseng CH, Eton O, Buzaid CA. Unexpected cytokines in serum of malignant melanoma patients during sequential biochemotherapy. Clin Cancer Res 2000; 6: 3895-3903.
Giri D, Ozen M, Ittmann M. Interleukin-6 is an autocrine growth factor in human prostate cancer. Am J Pathol 2001; 159: 2159-65.
Enewold L, Mechanic LE, Bowman ED, Zheng YL, Yu Z, Trivers G et al. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 2009; 18: 215-22.