Prognostic Value of Serum IL-18 and Nitric Oxide Activity in Breast Cancer Patients at Operable Stage

Abstract

Interleukin-18 (IL-18) is a multifunctional cytokine that was previously termed interferon-gamma-inducing factor. It has been suggested that serum IL-18 level may be used as a prognostic factor in some cancer types. Nitric oxide is a potent biologic molecule involved in the pathogenesis of cancer. In this study, we measured serum IL-18 and nitrate + nitrite levels in 56 patients with nonmetastatic breast cancer and 14 control subjects. Serum IL-18* and nitrate + nitrite** levels were significantly higher in patients with breast cancer when compared to the control subjects (*p < 0.05, **p < 0.001). Serum IL-18 levels were significantly higher in patients whose tumor size was greater than or equal to 5 cm when compared to patients whose tumor size was less than or equal to 2 cm (p < 0.05). Patients who were axillary lymph node negative (ALN) had lower serum IL-18 levels when compared to patients with positive ALN (p < 0.001). Serum IL-18 levels were significantly higher in patients with stage IIB or IIIA when compared to patients with stage I or IIA (p < 0.05). There was no significant difference in serum nitrate + nitrite levels in terms of age, tumor stage, estrogen receptor, and menopausal and ALN status (p > 0.05). In conclusion, serum IL-18 level may be a useful marker to predict prognosis of patients with breast cancer in complete remission after surgery. Long-term follow-up is required to clarify this hypothesis.

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

“…As mentioned above, it seems that NO is mostly produced in cancer cells by iNOS. Most investigators found an adverse prognostic significance for iNOS expression (28)(29)(30) and nitrotyrosine tumor staining (which reflects intracellular NO levels) (21), whereas there is no direct evidence from the literature for the prognostic significance of plasma/serum NO levels (31,32). In the present study, high plasma NO levels predicted poor survival only in univariate analysis, apparently because of their direct correlation with the number of involved organs.…”

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

“…21 Nonetheless, IL-18 is increased in the circulation of patients with different types of cancer. [22][23][24][25][26] Intriguingly, in an experimental tumor model, IL-18 mediated tumor progression through the enhancement of cancer cells' adhesive properties to the vascular endothelium or through proangiogenic activity. 27 Thus, the role of IL-18 in tumor biology and therapy remains a controversial issue.…”

Human pancreatic carcinoma cells secrete bioactive interleukin-18 after treatment with 5-fluorouracil: Implications for anti-tumor immune response

“…3 Here we report elevated serum levels of bioactive IL-18 in patients afflicted with pancreatic carcinoma. In fact, elevated serum levels of IL-18 have been observed in other tumors including colon carcinoma, 55 lung cancer, 55 hematological malignancies, including myeloma, 56,57 breast cancer, 58,59 gastric carcinoma, 60 esophageal carcinoma, 61 bladder cancer, 62 renal cell carcinoma 63 and head and neck carcinoma. 64 Generally, IL-18 production has been linked to aggressive tumor development and shorter survival times.…”