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Circulating soluble advanced glycation end product is inversely associated with the significant risk of developing cancer: evidence from a meta-analysis

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Tumor Biology

Abstract

Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: −373.77 to −70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = −87.62; 95 % CI: −138.60 to −36.63; P = 0.001) with improved heterogeneity (I 2 = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = −231.34; 95 % CI: −450.10 to −12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: −67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function.

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References

  1. Ramasamy R, Yan SF, Schmidt AM. Receptor for age (rage): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann N Y Acad Sci. 2011;1243:88–102.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Brodeur MR, Bouvet C, Bouchard S, Moreau S, Leblond J, Deblois D, et al. Reduction of advanced-glycation end products levels and inhibition of rage signaling decreases rat vascular calcification induced by diabetes. PLoS One. 2014;9:e85922.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Sorci G, Riuzzi F, Giambanco I, Donato R. Rage in tissue homeostasis, repair and regeneration. Biochim Biophys Acta. 1833;2013:101–9.

    Google Scholar 

  4. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. Hmgb1 and rage in inflammation and cancer. Annu Rev Immunol. 2010;28:367–88.

    Article  CAS  PubMed  Google Scholar 

  5. Pan H, Niu W, He L, Wang B, Cao J, Zhao F, et al. Contributory role of five common polymorphisms of rage and ape1 genes in lung cancer among han chinese. PLoS One. 2013;8:e69018.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Riehl A, Nemeth J, Angel P, Hess J. The receptor rage: Bridging inflammation and cancer. Cell Commun Signal CCS. 2009;7:12.

    Article  PubMed  Google Scholar 

  7. Arumugam T, Logsdon CD. S100p: a novel therapeutic target for cancer. Amino Acids. 2011;41:893–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, et al. Rage (receptor for advanced glycation endproducts), rage ligands, and their role in cancer and inflammation. J Transl Med. 2009;7:17.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Logsdon CD, Fuentes MK, Huang EH, Arumugam T. Rage and rage ligands in cancer. Curr Mol Med. 2007;7:777–89.

    Article  CAS  PubMed  Google Scholar 

  10. Yamagishi S, Adachi H, Nakamura K, Matsui T, Jinnouchi Y, Takenaka K, et al. Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects. Metab Clin Exp. 2006;55:1227–31.

    Article  CAS  PubMed  Google Scholar 

  11. Tesarova P, Kalousova M, Jachymova M, Mestek O, Petruzelka L, Zima T. Receptor for advanced glycation end products (RAGE)–soluble form (sRAGE) and gene polymorphisms in patients with breast cancer. Cancer Invest. 2007;25:720–5.

    Article  CAS  PubMed  Google Scholar 

  12. Piperis M, Provatopoulou X, Sagkriotis A, Kalogera E, Ampatzoglou E, Zografos GC, et al. Effect of breast cancer adjuvant therapies on potential biomarkers of pulmonary inflammation. Anticancer Res. 2012;32:4993–5002.

    CAS  PubMed  Google Scholar 

  13. Moy KA, Jiao L, Freedman ND, Weinstein SJ, Sinha R, Virtamo J, et al. Soluble receptor for advanced glycation end products and risk of liver cancer. Hepatology. 2013;57:2338–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9. W264.

    Article  PubMed  Google Scholar 

  15. DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28:105–14.

    Article  PubMed  Google Scholar 

  16. Bowden J, Tierney JF, Copas AJ, Burdett S. Quantifying, displaying and accounting for heterogeneity in the meta-analysis of rcts using standard and generalised Q statistics. BMC Med Res Methodol. 2011;11:41.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Germanova A, Tesarova P, Jachymova M, Zvara K, Zima T, Kalousova M. Glyoxalase i glu111ala polymorphism in patients with breast cancer. Cancer Invest. 2009;27:655–60.

    Article  CAS  PubMed  Google Scholar 

  18. Jing R, Cui M, Wang J, Wang H. Receptor for advanced glycation end products (RAGE) soluble form (sRAGE): a new biomarker for lung cancer. Neoplasma. 2010;57:55–61.

    Article  CAS  PubMed  Google Scholar 

  19. Krechler T, Jachymova M, Mestek O, Zak A, Zima T, Kalousova M. Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of rage and glyoxalase I genes in patients with pancreas cancer. Clin Biochem. 2010;43:882–6.

    Article  CAS  PubMed  Google Scholar 

  20. Jiao L, Taylor PR, Weinstein SJ, Graubard BI, Virtamo J, Albanes D, et al. Advanced glycation end products, soluble receptor for advanced glycation end products, and risk of colorectal cancer. Cancer Epidemiol Biomark Prev. 2011;20:1430–8.

    Article  CAS  Google Scholar 

  21. Jiao L, Weinstein SJ, Albanes D, Taylor PR, Graubard BI, Virtamo J, et al. Evidence that serum levels of the soluble receptor for advanced glycation end products are inversely associated with pancreatic cancer risk: a prospective study. Cancer Res. 2011;71:3582–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Stoetzer OJ, Fersching DM, Salat C, Steinkohl O, Gabka CJ, Hamann U, et al. Circulating immunogenic cell death biomarkers hmgb1 and rage in breast cancer patients during neoadjuvant chemotherapy. Tumour Biol. 2013;34:81–90.

    Article  CAS  PubMed  Google Scholar 

  23. Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010;2:1184–95.

    Article  Google Scholar 

  24. Chen RC, Yi PP, Zhou RR, Xiao MF, Huang ZB, Tang DL, Huang Y, Fan XG: The role of hmgb1-rage axis in migration and invasion of hepatocellular carcinoma cell lines. Mol Cell Biochem 2014

  25. Grote VA, Nieters A, Kaaks R, Tjonneland A, Roswall N, Overvad K, et al. The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: acase-control study within the prospective epic cohort. Cancer Epidemiol Biomark Prev. 2012;21:619–28.

    Article  CAS  Google Scholar 

  26. Nakamura K, Yamagishi S, Adachi H, Matsui T, Kurita-Nakamura Y, Takeuchi M, et al. Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating ages and soluble form of VCAM-1 in patients with type 2 diabetes. Microvasc Res. 2008;76:52–6.

    Article  CAS  PubMed  Google Scholar 

  27. Tang TT, Yuan J, Zhu ZF, Zhang WC, Xiao H, Xia N, et al. Regulatory t cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol. 2012;107:232.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Project of Department of Education of Heilongjiang Province (12531780). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Basic Medical Science College, Qiqihar Medical University, Bukui North Street 333, Jianhua District, Qiqihar, 161006, Heilongjiang, China

    Lan He, Jing Xue, Lihong Zheng, Qi Zhang, Lei Sun & Hongming Pan

  2. Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China

    Hongguang Bao

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  1. Lan He
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  2. Hongguang Bao
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  3. Jing Xue
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  4. Lihong Zheng
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  5. Qi Zhang
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  7. Hongming Pan
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Correspondence to Hongming Pan.

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He, L., Bao, H., Xue, J. et al. Circulating soluble advanced glycation end product is inversely associated with the significant risk of developing cancer: evidence from a meta-analysis. Tumor Biol. 35, 8749–8755 (2014). https://doi.org/10.1007/s13277-014-2122-7

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  • DOI: https://doi.org/10.1007/s13277-014-2122-7

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