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      A meta-analysis of CXCL12 expression for cancer prognosis

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          Abstract

          Background:

          CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed.

          Methods:

          We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival.

          Results:

          Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17–1.65, P=0.0002) and 1.12 (95% CI: 0.82–1.53, P=0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31–3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21–1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08–1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38–0.66, P<0.00001).

          Conclusions:

          Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective–retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.

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          Most cited references49

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          The metastatic niche: adapting the foreign soil.

          The 'seed and soil' hypothesis for metastasis sets forth the concept that a conducive microenvironment, or niche, is required for disseminating tumour cells to engraft distant sites. This Opinion presents emerging data that support this concept and outlines the potential mechanism and temporal sequence by which changes occur in tissues distant from the primary tumour. To enable improvements in the prognosis of advanced malignancy, early interventions that target both the disseminating seed and the metastatic soil are likely to be required.
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            Chemokines in cancer.

            Chemokines are chemotactic cytokines that control the migration of cells between tissues and the positioning and interactions of cells within tissue. The chemokine superfamily consists of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane spanning signaling receptors. Chemokines mediate the host response to cancer by directing the trafficking of leukocytes into the tumor microenvironment. This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and protumor activities. Although chemokines were initially appreciated as important mediators of immune cell migration, we now know that they also play important roles in the biology of nonimmune cells important for tumor growth and progression. Chemokines can directly modulate the growth of tumors by inducing the proliferation of cancer cells and preventing their apoptosis. They also direct tumor cell movement required for metastasis. Chemokines can also indirectly modulate tumor growth through their effects on tumor stromal cells and by inducing the release of growth and angiogenic factors from cells in the tumor microenvironment. In this Masters of Immunology primer, we focus on recent advances in understanding the complex nature of the chemokine system in tumor biology with a focus on how the chemokine system could be used to augment cancer immunotherapeutic strategies to elicit a more robust and long-lasting host antitumor immune response.
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              Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone.

              Neoplasms have a striking tendency to metastasize or "home" to bone. Hematopoietic cells also home to bone during embryonic development, where evidence points to the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12; expressed by osteoblasts and endothelial cells) and its receptor (CXCR4) as key elements in these processes. We hypothesized that metastatic prostate carcinomas also use the SDF-1/CXCR4 pathway to localize to the bone. To test this, levels of CXCR4 expression were determined for several human prostate cancer cell lines by reverse transcription-PCR and Western blotting. Positive results were obtained for cell lines derived from malignancies that had spread to bone and marrow. Prostate cancer cells were also observed migrating across bone marrow endothelial cell monolayers in response to SDF-1. In in vitro adhesion assays, pretreatment of the prostate cancer cells with SDF-1 significantly increased their adhesion to osteosarcomas and endothelial cell lines in a dose-dependent manner. Invasion of the cancer cell lines through basement membranes was also supported by SDF-1 and inhibited by antibody to CXCR4. Collectively, these results suggest that prostate cancers and perhaps other neoplasms may use the SDF-1/CXCR4 pathway to spread to bone.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                27 June 2017
                23 May 2017
                : 117
                : 1
                : 124-135
                Affiliations
                [1 ]Medical Sciences Division, University of Oxford , Oxford, UK
                [2 ]CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford , Oxford, UK
                [3 ]Cairns Library, John Radcliffe Hospital , Oxford, UK
                [4 ]Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Trust , Oxford, UK
                [5 ]Nuffield Department of Surgical Sciences, University of Oxford , Room 6607, Level 6, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
                Author notes
                Article
                bjc2017134
                10.1038/bjc.2017.134
                5520200
                28535157
                7ed8728d-76ba-4eb0-a66d-546e107c90e5
                Copyright © 2017 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 18 January 2017
                : 08 April 2017
                : 24 April 2017
                Categories
                Genetics & Genomics

                Oncology & Radiotherapy
                metastasis,survival,recurrence,prognosis,cxcl12,sdf1,chemokine,cytokine
                Oncology & Radiotherapy
                metastasis, survival, recurrence, prognosis, cxcl12, sdf1, chemokine, cytokine

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