Serum IL-8 level as a candidate prognostic marker of response to anti-angiogenic therapy for metastatic colorectal cance
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ORIGINAL ARTICLE
Serum IL-8 level as a candidate prognostic marker of response to anti-angiogenic therapy for metastatic colorectal cancer Mitsukuni Suenaga 1,2 & Tetsuo Mashima 3 & Naomi Kawata 1,3 & Takeru Wakatsuki 1 & Shingo Dan 4 & Hiroyuki Seimiya 3 & Kensei Yamaguchi 1 Accepted: 8 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Liver metastasis (LM) is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC). Here, we investigated the prognostic utility of several serum factors in mCRC patients with or without LM who were treated with antiangiogenic agents in first-line (FL) or salvage-line (SL) settings. Methods A combined cohort of 125 patients was analyzed in this single institute pooled analysis: FL cohort receiving bevacizumab (n = 71) and SL cohort receiving regorafenib (n = 54). Blood samples were obtained at baseline (BL) and during treatment, and serum factors were measured by ELISA. Overall survival (OS) was analyzed using Kaplan–Meier curves, the logrank test, and Cox proportional hazard regression methods. Results In univariate analysis of the combined cohort, right-sided CRC, primary unresected tumor, wild-type KRAS, LM, ≥ 2 metastatic sites, and SL were associated with shorter OS; in multivariable analysis, LM and SL remained significant. Serum angiopoietin-2 (Ang-2) levels ≥ 2190.3 pg/ml and interleukin (IL)-8 levels ≥ 15.1 pg/ml at BL were significantly associated with LM. Using these cut-off values, patients with higher Ang-2 or IL-8 levels at BL had shorter OS than those with lower BL levels (Ang-2: hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.47–4.51, P = 0.001; IL-8: HR 4.31, 95%CI 2.11–8.79, P < 0.001). High serum IL-8 level remained a significant predictor of shorter OS in multivariable analysis (HR 3.24, 95%CI 1.47– 7.16, P = 0.004). Conclusion Circulating IL-8 and Ang-2 levels are associated with LM in mCRC patients. IL-8 may be a prognostic marker of response to anti-angiogenic therapy, regardless of the treatment timing. Keywords IL-8 . Tumor microenvironment . Angiogenesis . Liver metastasis . Metastatic colorectal cancer
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00384-020-03748-y) contains supplementary material, which is available to authorized users. * Mitsukuni Suenaga [email protected] 1
Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan
2
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
3
Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan
4
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135–8550, Japan
Introduction Reliable, predicti
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