Advertisement

Matrix Metalloproteinase-2 Single Nucleotide Polymorphism in Egyptian Non-Hodgkin Lymphoma Patients: Correlation with Clinicopathological Characteristics and Outcome

  • Rania M. Bakry
  • Ebtesam M. El-Gezawy
  • Abeer M. Darwish
  • Eman NasrEldin
  • Noha Gaber
  • Khalid A. Nasif
  • EssamAbd El-Mohsen
  • Salma Mahfouz
Original Article
  • 20 Downloads

Abstract

Non-Hodgkin’s lymphoma (NHL) is an exceedingly diversified group of lymphoproliferative neoplasms emerging from B-, T- or natural killer -lymphocytes. This study was done to detect Matrix metalloproteinase-2 (MMP2)-735C/T gene polymorphism in patients with NHL and its relation to the clinicopathological characteristics of the studied patients in addition to detection the association between it and NHL disease susceptibility and progression. Clinico-hematological profiles were done on 50 NHL patients. The genotypes and allelic frequencies of MMP-2 polymorphisms were recognized utilizing Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP). PCR products after adding restriction endonuclease were analyzed using QIAxcel advanced (automated) instrument. The CT + TT genotypes and T allele of MMP2 735C/T were statistically significant in patients having advanced clinical stages III/IV compared to patients with stages I/II. Another significance was observed in patients with intermediate high/high IPI score and BM infiltration. Interestingly, patients with MMP2-735C/T genotype exhibit lower rate of survival. Our results demonstrated that MMP2-735C/T polymorphism may potentially affect the progression of NHL. Further larger scale studies are needed.

Keywords

Non hodjkin lymphoma Matrix metalloproteinase-2 Polymorphism 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Wróbel T, Mazur G, Dzietczenia J, Gębura K, Kuliczkowski K (2013) Bogunia-Kubik K (2013) VEGF and bFGF gene polymorphisms in patients with non-Hodgkin's lymphoma. Biomed Res Int 2013:159813.  https://doi.org/10.1155/2013/159813 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, (2002). CA Cancer J Clin 55:74–108CrossRefGoogle Scholar
  3. 3.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F GLOBOCAN (2012) v1.0. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, IARC, 2013Google Scholar
  4. 4.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63(1):11–30CrossRefGoogle Scholar
  5. 5.
    Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al. (eds) (2007) Cancer incidence in five continents, vol IX. IARC Scientific Publication No. 160. http://gco.iarc.fr
  6. 6.
    Herzog CM, Dey S, Hablas A, Khaled HM, Seifeldin IA, Ramadan M, El-Hamzawy H, Wilson ML, Soliman AS (2012) Geographic distribution of hematopoietic cancers in the Nile delta of Egypt. Ann Oncol 23:2748–2755CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A (2014) Cancer treatment and survivorship statistics, 2014: Cancer Treatment and Survivorship Statistics, 2014. CA A Cancer J Clin 64:252–271CrossRefGoogle Scholar
  8. 8.
    Hadler-Olsen E, Winberg JO, Uhlin-Hansen L (2013) Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. TumourBiol 34:2041–2051Google Scholar
  9. 9.
    Butler GS, Overall CM (2009) Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting. Nat Rev Drug Discov 8:935–948CrossRefPubMedGoogle Scholar
  10. 10.
    Yu C, Zhou Y, Miao X et al (2004) Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. Cancer Res 64:7622–7628CrossRefPubMedGoogle Scholar
  11. 11.
    Sag SO, Gorukmez O, Ture M, Gorukmez O, Topak A, Sahinturk S, Ocakoglu G, Gulten T, Ali R, Yakut T (2015) MMP2 gene-735 C/T and MMP9 gene -1562 C/T polymorphisms in JAK2V617F positive myeloproliferative disorders. Asian Pac J Cancer Prev 16:443–449CrossRefPubMedGoogle Scholar
  12. 12.
    Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42:113–185CrossRefPubMedGoogle Scholar
  13. 13.
    Shen W, Xi H, Wei B, Chen L (2014) The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis. J Cancer Res Clin Oncol 140:1003–1009CrossRefPubMedGoogle Scholar
  14. 14.
    Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:Ra32–Ra40PubMedGoogle Scholar
  15. 15.
    Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y et al (2010) The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest 28:661–669CrossRefPubMedGoogle Scholar
  16. 16.
    Van der Jagt MF, Wobbes T, Strobbe LJ, Sweep FC, Span PN (2010) Metalloproteinases and their regulators in colorectal cancer. J Surg Oncol 101:259–269PubMedGoogle Scholar
  17. 17.
    Gadducci A, Cosio S, Tana R, Genazzani AR (2009) Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer. Crit Rev Oncol Hematol 69:12–27CrossRefPubMedGoogle Scholar
  18. 18.
    Travaglino E, Benatti C, Malcovati L et al (2008) Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute myeloid leukaemias and myelodysplastic syndromes. Eur J Haematol 80:216–226CrossRefPubMedGoogle Scholar
  19. 19.
    Buggins AG, Levi A, Gohil S et al (2011) Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9. Br J Haematol 154:216–222CrossRefPubMedGoogle Scholar
  20. 20.
    Kuittinen O, Savolainen ER, Koistinen P, Möttönen M, Turpeenniemi-Hujanen T (2001) MMP-2 and MMP-9 expression in adult and childhood acute lymphatic leukemia (ALL). Leuk Res 25:125–131CrossRefPubMedGoogle Scholar
  21. 21.
    Diao LP, Ma H, Wei GC, Li T, Liu HS, Liu LH, Wu LL, Zhao GM, Gao YH (2012) Matrix metalloproteinase-2 promoter and tissue inhibitor of metalloproteinase-2 gene polymorphisms in non-Hodgkin’s lymphoma. Int J Cancer 131(5):1095–1103CrossRefPubMedGoogle Scholar
  22. 22.
    Gouda HM, Khorshied MM, El Sissy MH, Shaheen IAM, Mohsen MMA (2014) Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin’s lymphoma in Egyptians. Ann Hematol 93:1313–1318PubMedGoogle Scholar
  23. 23.
    Vasku A, Vasku JB, Necas M, Vasku V (2010) Matrix Metalloproteinase-2 promoter genotype as a marker of cutaneous T-cell lymphoma early stage. J Biomed Biotechnol 2010:805907CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhou Y, Yu C, Miao X, Wang Y, Tan W, Sun T, Zhang X, Xiong P, Lin D (2005) Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancersusceptibility. Carcinogenesis 26:1117–1121CrossRefPubMedGoogle Scholar
  25. 25.
    Rollin J, Régina S, Vourc’h P, Iochmann S, Bléchet C, Reverdiau P, Gruel Y (2007) Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer. Lung Cancer 56:273–280CrossRefPubMedGoogle Scholar
  26. 26.
    Miao X, Yu C, Tan W, Xiong P, Liang G, Lu W, Lin D (2003) A functional polymorphism in the matrix metalloproteinase-2 gene promoter (− 1306C/T) is associated with risk of development but not metastasis of gastric cardia adenocarcinoma. Cancer Res 63:3987–3990PubMedGoogle Scholar
  27. 27.
    Ghilardi G, Biondi ML, Caputo M, Leviti S, DeMonti M, Guagnellini E, Scorza R (2002) A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility. Clin Cancer Res 8:3820–3823PubMedGoogle Scholar
  28. 28.
    Kelly T, Borset M, Abe E et al (2000) Matrix metalloproteinases in multiple myeloma. Leuk Lymphoma 37(3–4):273–281CrossRefPubMedGoogle Scholar
  29. 29.
    Thomas KH, Myen P, Suttorp N (2006) Single nucleotide polymorphismin 5′-flankingregion reduces transcription of surfactant protein B gene in H441 cells. Am J Physiol Lung Cell Mol Physiol 291(3):L386–L390CrossRefPubMedGoogle Scholar
  30. 30.
    Zysow BR, Lindahl GE, Wade DP, Knight BL, Lawn RM (1995) C/T polymorphism in the 5′ untranslated region of the apolipoprotein(a) gene introduces an upstream ATG and reduces in vitro translation. Arterioscler Thromb Vasc Biol 15(1):58–64CrossRefPubMedGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2018

Authors and Affiliations

  • Rania M. Bakry
    • 1
  • Ebtesam M. El-Gezawy
    • 2
  • Abeer M. Darwish
    • 1
  • Eman NasrEldin
    • 2
  • Noha Gaber
    • 1
  • Khalid A. Nasif
    • 3
  • EssamAbd El-Mohsen
    • 4
  • Salma Mahfouz
    • 1
  1. 1.Oncological Clinical Pathology Department, South Egypt Cancer InstituteAssiut UniversityAssiutEgypt
  2. 2.Clinical Pathology Department, Faculty of MedicineAssiut UniversityAssiutEgypt
  3. 3.Biochemistry Department, Faculty of MedicineMinya UniversityMinyaEgypt
  4. 4.Internal Medicine Department, Faculty of MedicineAssiut UniversityAssiutEgypt

Personalised recommendations