IL-32 expression is an independent prognostic marker for gastric cancer
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ORIGINAL PAPER
IL-32 expression is an independent prognostic marker for gastric cancer Sumiya Ishigami • Takaaki Arigami • Yasuto Uchikado • Tetsuro Setoyama Yoshiaki Kita • Ken Sasaki • Hiroshi Okumura • Hiroshi Kurahara • Yuko Kijima • Aya Harada • Shinichi Ueno • Shoji Natsugoe
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Received: 10 December 2012 / Accepted: 15 January 2013 / Published online: 12 March 2013 Ó Springer Science+Business Media New York 2013
Abstract A strong link between inflammation and gastrointestinal cancer has been demonstrated. Interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor kappa B (NF-jB) activation. We investigated whether IL-32 expression has clinical significance in gastric cancer. A total of 182 gastric cancer patients who received curative gastrectomy were enrolled in our study. IL-32 expression was detected by immunohistochemistry, and the correlation between clinicopathological features and IL-32 expression was analyzed. Tumor depth and lymph node metastases developed more frequently in IL-32-positive gastric cancer patients than those who were negative for IL-32 expression (p \ 0.01). Lymphatic- and venous invasion in the IL-32-positive group were more severe than in cancer cells lacking IL-32 expression (p \ 0.05). Multivariate analysis demonstrated that IL-32 is one of the prognostic markers (p \ 0.03) for gastric cancer, in addition to nodal involvement and tumor depth. IL-32 positivity significantly affected clinicopathological factors. Thus, IL-32 expression in gastric cancer may serve as a preferential metastatic condition that allows cells to escape host antitumor immunity. Pro-inflammatory cytokines induce immunosuppression in a paracrine manner, thereby facilitating the metastasis of tumor cells. Keywords IL-32 Pro-inflammatory cytokine Prognostic marker Lymph node Gastric cancer
S. Ishigami (&) T. Arigami Y. Uchikado T. Setoyama Y. Kita K. Sasaki H. Okumura H. Kurahara Y. Kijima A. Harada S. Ueno S. Natsugoe Digestive Surgery Surgical Oncology, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JAPAN e-mail: [email protected]
Introduction Gastric cancer is one of the major causes of cancer-induced mortality worldwide, especially in Eastern Asian countries [1–3]. Due to the prevalence of mass screening for gastric cancer, malignant stomach lesions can be detected in early stages by gastrointestinal fibroscopy. When these gastric cancer patients receive curative surgery or endoscopic treatment [4], a favorable prognosis can be expected; however, despite undergoing curative resection for early stage gastric cancer, some patients show an unfavorable postoperative course [5]. Generally, tumor node metastasis (TNM) factors are the strongest prognostic markers for gastrointestinal cancer [6, 7]. In addition to TNM factors, it has been reported that biological markers, including inflammatory cytokines such as IL-1, IL-6, and IL-10, also affect gastric carcinoma prognosis [
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