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CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer

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Tumor Biology

Abstract

The CXCL12-CXCR4 axis is proposed to mediate metastasis formation. In this study, we examined CXCL12, CXCR4 and the relative CXCL12-CXCR4 expression as prognostic factors in two cohorts of colon cancer patients. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to study CXCR4, CXCL12 and relative CXCL12-CXCR4 expression in tissue microarrays. Our study included totally 596 patients, 290 in cohort 1 and 306 in cohort 2. For tumour, node, metastasis (TNM) stage III, low nuclear expression of CXCR4 was a positive prognostic factor for 5-year disease-free survival (DFS) in cohort 1 (P = 0.007) and cohort 2 (P = 0.023). In multivariate analysis for stage III, nuclear expression of CXCR4 in cohort 1 was confirmed as a prognostic factor for DFS (hazard ratio (HR), 0.27; 95 % CI, 0.09 to 0.77). For TNM stage III, high cytoplasmic expression of CXCL12 was associated with better 5-year DFS in both cohorts (P = 0.006 and P = 0.006, respectively). We further validated the positive prognostic value of CXCL12 expression for 5-year DFS in stage III with ISH (P = 0.022). For TNM stage III, the relative CXCL12-CXCR4 expression (CXCL12 > CXCR4 vs CXCL12 = CXCR4 vs CXCL12 < CXCR4) was a prognostic factor for 5-year DFS in cohort 1 (92 % vs 46 % vs 31 %, respectively; P < 0.001) and cohort 2 (92 % vs 66 % vs 30 %, respectively; P = 0.006). In conclusion, CXCL12 and relative CXCL12-CXCR4 expression are independent prognostic factors for 5-year DFS in TNM stage III colon cancer.

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Acknowledgments

This work was supported by Norwegian Cancer Society grant (grant no. 422146). The study was also supported by Haraldsplass Deaconess Hospital and Health Region West. We thank Christine Drengenes, Benedikte Rosenlund and Yvonne Muller for excellent technical assistance.

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Authors and Affiliations

  1. Section of Oncology, Department of Clinical Science, University of Bergen, Post box 7804, 5020, Bergen, Norway

    Luka Stanisavljević & Olav Dahl

  2. Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway

    Jörg Aßmus

  3. Department of Surgery, Haraldsplass Deaconess Hospital, Bergen, Norway

    Kristian Eeg Storli

  4. Department of Pathology, Haukeland University Hospital, Bergen, Norway

    Sabine Maria Leh

  5. Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Sabine Maria Leh

  6. Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway

    Olav Dahl & Mette Pernille Myklebust

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  1. Luka Stanisavljević
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  4. Sabine Maria Leh
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Correspondence to Luka Stanisavljević.

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Stanisavljević, L., Aßmus, J., Storli, K.E. et al. CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer. Tumor Biol. 37, 7441–7452 (2016). https://doi.org/10.1007/s13277-015-4591-8

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  • DOI: https://doi.org/10.1007/s13277-015-4591-8

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