Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma

Masaharu Ogura, Hiroya Takeuchi, Hirofumi Kawakubo, Tomohiko Nishi, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Yoshiro Saikawa, Tai Omori, Taku Miyasho, Shingo Yamada, Yuko Kitagawa

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Abstract

Background CXCL-8, known as proinflammatory cytokine interleukin (IL)-8, and its receptor, CXCR-2, are expressed in various cancer cells. CXCL-8/CXCR-2 network is believed to be involved in angiogenesis, growth, and invasion of tumor cells. To date, the clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we investigated the role of CXCL- 8/CXCR-2 network in ESCC. Methods The subjects included 78 patients with primary ESCC. We examined CXCL-8 and CXCR-2 expression in surgically resected specimens using immunohistochemistry. The association between CXCL-8/CXCR-2 expression and level of preoperative serum cytokines, C-reactive protein (CRP), coagulation factors, clinicopathologic background factors, and survival of ESCC patients was assessed. Results Thirty-seven (47%) and 36 (46%) patients were positive for CXCL-8 and CXCR-2 expression, respectively. Both CXCL-8 and CXCR-2 were expressed in 26 patients (33%). We compared the results of these 26 patients [CXCL-8(+)/CXCR-2(+) group] with those of the other group (n = 52). The depth of invasion (pT factor; P <.001), lymph node metastasis (pN factor; P =.001), pathologic stage (P <.001), lymphatic invasion (P =.010), and venous invasion (P =.001) were significantly more advanced in the CXCL-8(+)/CXCR-2(+) group compared with the other group. Preoperative IL-6, IL-8, CRP, fibrin/fibrinogen degradation product, and fibrinogen levels in the CXCL-8(+)/CXCR-2(+) group were also significantly higher than those in the other group (P =.046,.009,.029,.010, and <.001, respectively). The CXCL-8(+)/CXCR-2(+) group also showed a significantly lower recurrence-free survival (RFS; P <.001) and disease-specific survival (P =.008). As per Cox's hazards model, CXCL-8/CXCR-2 expression (hazard ratio, 2.89; P =.008) was independent predictive factor for RFS. Conclusion Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression, metastasis, higher preoperative levels of proinflammatory cytokines, CRP, activation of exogenous coagulation factors, and poor prognosis in ESCC patients. These results indicate that overexpression of both CXCL-8 and CXCR-2 may be a useful marker for predicting the outcome in ESCC patients, and more important, has potential in becoming a critical diagnostic marker for selection of appropriate treatments.

Original languageEnglish
Pages (from-to)512-520
Number of pages9
JournalSurgery (United States)
Volume154
Issue number3
DOIs
Publication statusPublished - 2013 Sep 1

ASJC Scopus subject areas

  • Surgery

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    Ogura, M., Takeuchi, H., Kawakubo, H., Nishi, T., Fukuda, K., Nakamura, R., Takahashi, T., Wada, N., Saikawa, Y., Omori, T., Miyasho, T., Yamada, S., & Kitagawa, Y. (2013). Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma. Surgery (United States), 154(3), 512-520. https://doi.org/10.1016/j.surg.2013.06.013