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Serum Chemokine Ligand 5 (CCL5/RANTES) Level Might be Utilized as a Predictive Marker of Tumor Behavior and Disease Prognosis in Patients with Gastric Adenocarcinoma

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Abstract

Purpose

Gastric cancer is the second leading cause of cancer-related deaths worldwide and the most common gastrointestinal cancer in Iran. Chemokine ligand 5 (CCL5/RANTES) is one of the most potent angiogenic factors that plays an important role in tumor growth, invasion, and metastasis. We aimed to assess the serum level of CCL5 in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prognosis.

Methods

Seventy-four patients with gastric adenocarcinoma that had undergone gastrectomy and 96 non-tumoral cases in which gastric cancer was ruled out by gastroscopy and biopsy were enrolled. Demographic and epidemiological characteristics and patient survival data were reviewed. Histological type, grade, and tumor stage (TNM) were determined by a single expert pathologist. Helicobacter pylori infection status and CCL5 serum level were measured by ELISA. Data were analyzed using SPSS software version 16.

Results

Patients with gastric adenocarcinoma had significantly higher serum CCL5 level compared with control group (P < .001). Higher serum CCL5 levels were associated with lower histological differentiation (P < .001), higher depth of tumor invasion (P = .022), more frequent lymph nodes involvement (P = .028), and advanced tumor stage (P = .002). The overall survival of patients with CCL5 levels higher than 70,671 pg/ml was significantly lower than those with lower than this cutoff (P = .043).

Conclusions

Serum CCL5 levels might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma. Further studies to assess tissue expression of CCL5 and its gene polymorphisms are suggested.

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References

  1. Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77.

    Article  PubMed  Google Scholar 

  2. Malekzadeh R, Derakhshan M, Malekzadeh Z. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009;12(6):576–83.

    PubMed  Google Scholar 

  3. Schall TJ, Bacon KB. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol. 1994;6(6):865–73.

    Article  CAS  PubMed  Google Scholar 

  4. Balkwill F. Chemokine biology in cancer. Semin Immunol. 2007;15(1):49–55.

    Article  Google Scholar 

  5. Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nat. 2001;410(6824):50–6.

    Article  Google Scholar 

  6. Murphy P. Chemokines and the molecular basis of cancer metastasis. N Engl J Med. 2001;345(11):833–5.

    Article  CAS  PubMed  Google Scholar 

  7. Singh S, Sadanandam A, Singh R. Chemokines in tumor angiogenesis and metastasis. Cancer Metastasis Rev. 2007;26(3–4):453–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Luboshits G, Shina S, Kaplan O, Engelberg S, Nass D, Lifshitz-Mercer B, et al. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 1999;59(18):4681–7.

    CAS  PubMed  Google Scholar 

  9. Azenshtein E, Luboshits G, Shina S, Neumark E, Shahbazian D, Weil M, et al. The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res. 2002;62(4):1093–102.

    CAS  PubMed  Google Scholar 

  10. Robinson SC, Scott KA, Wilson JL, Thompson RG, Proudfoot AE, Balkwill FR. A chemokine receptor antagonist inhibits experimental breast tumor growth. Cancer Res. 2003;63(23):8360–5.

    CAS  PubMed  Google Scholar 

  11. Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY. Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Nat Cancer Inst. 2005;17(1):51–5.

    PubMed  Google Scholar 

  12. Yaal-Hahoshen N, Shina S, Leider-Trejo L, Barnea I, Shabtai EL, Azenshtein E, et al. The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clin Cancer Res. 2006;12(15):4474–8.

    Article  CAS  PubMed  Google Scholar 

  13. Niwa Y, Akamatsu H, Niwa H. Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer. Clin Cancer Res. 2001;7(2):285–9.

    CAS  PubMed  Google Scholar 

  14. Tsukishiro S, Suzumori N, Nishikawa H. Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder. Gynecol Oncol. 2006;102(3):542–5.

    Article  CAS  PubMed  Google Scholar 

  15. Vaday GG, Peehl DM, Kadam PA, Lawrence DM. Expression of CCL5 (RANTES) and CCR5 in prostate cancer. Prostate. 2006;66(2):124–34.

    Article  CAS  PubMed  Google Scholar 

  16. Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, et al. Elevated levels of circulating platelet micro particles. VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer. 2003;39(2):184–91.

    Article  CAS  PubMed  Google Scholar 

  17. Okita K, Furuhata T, Kimura Y, Kawakami M, Yamaguchi K, Tsuruma T, et al. The interplay between gastric cancer cell lines and PBMCs mediated by the CC chemokine RANTES plays an important role in tumor progression. J Exp Clin Cancer Res. 2005;24(3):439–46.

    CAS  PubMed  Google Scholar 

  18. Sugasawa H, Ichikura T, Tsujimoto H, Kinoshita M, Morita D, Ono S, et al. Prognostic significance of expression of CCL5/RANTES receptors in patients with gastric cancer. J Surg Oncol. 2008;97(5):445–5.

    Article  PubMed  Google Scholar 

  19. Sugasawa H, Ichikura T, Kinoshita M, Ono S, Majima T, Tsujimoto H, et al. Gastric cancer cells exploit CD4+ cell-derived CCL5 for their growth and prevention of CD8+ cell-involved tumor elimination. Int J Cancer. 2008;122(11):2535–41.

    Article  CAS  PubMed  Google Scholar 

  20. Stolte M, Meining A. The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol. 2001;15:591.

    CAS  PubMed  Google Scholar 

  21. Green FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.

    Book  Google Scholar 

  22. Sadjadi A, Malekzadeh R, Derakhshan MH, Sepehr A, Nouraie M, Sotoudeh M, et al. Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer. 2003;107(1):113–8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This paper has been written according to the result of the residency thesis of the first author. This study was supported by a grant (No. 88042) from Mashhad University of Medical Sciences. We would like to thank Dr. Abbas Esmaeilzadeh as well as our colleagues in Gastric Cancer Research Group and in the Endoscopy Unit of Imam Reza Hospital for their great cooperation.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Science, Tehran, 14117, Iran

    Ali Reza Sima

  2. Department of Medicine, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10468, USA

    Hamid Reza Sima

  3. Inflammation and Inflammatory Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Houshang Rafatpanah & Narges Valizadeh

  4. Vice Chancellery for Health, Mashhad University of Medical Sciences, Mashhad, Iran

    Hanieh Hosseinnezhad

  5. Department of Pathology, Razavi Hospital, Mashhad, Iran

    Kamran Ghaffarzadehgan

  6. Surgical Oncology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mostafa Mehrabi Bahar

  7. Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamid Reza Hakimi

  8. School of Medicine, Islamic Azad University, Mashhad Branch, Mashhad, Iran

    Anahita Masoom

  9. School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amin Noorbakhsh & Nahid Razavi Satvati

  10. Department of Radiation Oncology, University of Toronto, Toronto, Canada

    Hamid Reza Raziee

Authors
  1. Ali Reza Sima
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  2. Hamid Reza Sima
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  3. Houshang Rafatpanah
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  4. Hanieh Hosseinnezhad
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  5. Kamran Ghaffarzadehgan
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  6. Narges Valizadeh
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  7. Mostafa Mehrabi Bahar
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  8. Hamid Reza Hakimi
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  9. Anahita Masoom
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  10. Amin Noorbakhsh
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  11. Nahid Razavi Satvati
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  12. Hamid Reza Raziee
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Corresponding author

Correspondence to Hamid Reza Sima.

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Sima, A.R., Sima, H.R., Rafatpanah, H. et al. Serum Chemokine Ligand 5 (CCL5/RANTES) Level Might be Utilized as a Predictive Marker of Tumor Behavior and Disease Prognosis in Patients with Gastric Adenocarcinoma. J Gastrointest Canc 45, 476–480 (2014). https://doi.org/10.1007/s12029-014-9652-5

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  • DOI: https://doi.org/10.1007/s12029-014-9652-5

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