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KIRs gene content diversity in Iranians with urothelial bladder cancer

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Abstract

Natural killer cells (NK) are the first arm of the innate immune system in defense against tumor and infection. 16 distinct Killer-cell immunoglobulin-like receptors (KIRs) are involved in orchestrating NK cell function. The KIR family contains 14 genes and 2 pseudogenes. Six of these receptors are activating (aKIR) and the remaining receptors are inhibitory KIRs (iKIR), that interact with MHC-I molecules; producing signals which stop NK cell function. In the current study, we have investigated the genomic diversity of KIRs and determining the A and B haplotypes as well as Bx subsets in 119 patients with bladder cancer and 200 healthy controls to find out if there is an association between KIR system and susceptibility to bladder cancer. Polymerase chain reaction with sequence specific primers (SSP–PCR) typing system was used to determine the KIR gene profile. The results implicated decreased frequency of inhibitory KIR2DL2 and activating KIR2DS2 while increased frequency of CxT4 genotypes in patients compared with healthy controls. Among Bx subsets, the CxT4 gene cluster is more frequent in bladder cancer patients compared to controls. Our results provide a conclusion that KIR2S2 and KIR2L2 may play a protective role against bladder cancer development while the CxT4 gene cluster may underlie susceptibility to bladder cancer in Iranian population.

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References

  1. Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63(2):234–241

    Article  PubMed  Google Scholar 

  2. Sexton WJ, Wiegand LR, Correa JJ, Politis C, Dickinson SI, Kang LC (2010) Bladder cancer: a review of non-muscle invasive disease. Cancer Control 17(4):256–268

    Article  PubMed  Google Scholar 

  3. Jacobs BL, Lee CT, Montie JE (2010) Bladder cancer in 2010: how far have we come? CA: Cancer J Clin 60 (4):244–272

    Google Scholar 

  4. Letašiová S, Medveďová A, Šovčíková A, Dušinská M, Volkovová K, Mosoiu C, Bartonová A (2012) Bladder cancer, a review of the environmental risk factors. Environ Health 11(S1):S11

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chu H, Wang M, Zhang Z (2013) Bladder cancer epidemiology and genetic susceptibility. J Biomed Res 27(3):170

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Tiwari JL, Terasaki PI (2012) HLA and disease associations. Springer, New York

    Google Scholar 

  7. Rajalingam R (2011) Human diversity of killer cell immunoglobulin-like receptors and disease. Korean J Hematol 46(4):216–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cooley S, Trachtenberg E, Bergemann TL, Saeteurn K, Klein J, Le CT, Marsh SG, Guethlein LA, Parham P, Miller JS (2009) Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood 113(3):726–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Manser AR, Weinhold S, Uhrberg M (2015) Human KIR repertoires: shaped by genetic diversity and evolution. Immunol Rev 267(1):178–196

    Article  CAS  PubMed  Google Scholar 

  10. Thielens A, Vivier E, Romagné F (2012) NK cell MHC class I specific receptors (KIR): from biology to clinical intervention. Curr Opin Immunol 24(2):239–245

    Article  CAS  PubMed  Google Scholar 

  11. Kulkarni S, Martin MP, Carrington M (2008) The Yin and Yang of HLA and KIR in human disease. Semin Immunol 20(6):343–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Middleton D, Vilchez J, Cabrera T, Meenagh A, Williams F, Halfpenny I, Maleno I, Ruiz-Cabello F, Lopez-Nevot M, Garrido F (2007) Analysis of KIR gene frequencies in HLA class I characterised bladder, colorectal and laryngeal tumours. HLA 69(3):220–226

    CAS  Google Scholar 

  13. Vilches C, Castano J, Gómez-Lozano N, Estefania E (2007) Facilitation of KIR genotyping by a PCR-SSP method that amplifies short DNA fragments. HLA 70(5):415–422

    CAS  Google Scholar 

  14. Ashouri E, Ghaderi A, Reed E, Rajalingam R (2009) A novel duplex SSP–PCR typing method for KIR gene profiling. HLA 74(1):62–67

    CAS  Google Scholar 

  15. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7(6):753–763

    Article  CAS  PubMed  Google Scholar 

  16. Moesta AK, Parham P (2012) Diverse functionality among human NK cell receptors for the C1 epitope of HLA-C: KIR2DS2, KIR2DL2, and KIR2DL3. Front Immunol. https://doi.org/10.3389/fimmu.2012.00336

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pyo C-W, Guethlein LA, Vu Q, Wang R, Abi-Rached L, Norman PJ, Marsh SG, Miller JS, Parham P, Geraghty DE (2010) Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus. PLoS ONE 5(12):e15115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180(6):3969–3979

    Article  CAS  PubMed  Google Scholar 

  19. Lin Z, Kuroki K, Kuse N, Sun X, Akahoshi T, Qi Y, Chikata T, Naruto T, Koyanagi M, Murakoshi H (2016) HIV-1 control by NK cells via reduced interaction between KIR2DL2 and HLA-C∗ 12: 02/C∗ 14: 03. Cell Rep 17(9):2210–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Augusto DG (2016) The impact of KIR polymorphism on the risk of developing cancer: not as strong as imagined? Front Genet 7:121

    Article  PubMed  PubMed Central  Google Scholar 

  21. Aguilar AMO, Guethlein LA, Adams EJ, Abi-Rached L, Moesta AK, Parham P (2010) Coevolution of killer cell Ig-like receptors with HLA-C to become the major variable regulators of human NK cells. J Immunol 185(7):4238–4251

    Article  PubMed Central  Google Scholar 

  22. Miyashita R, Tsuchiya N, Yabe T, Kobayashi S, Hashimoto H, Ozaki S, Tokunaga K (2006) Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis. Arthritis Rheumatol 54(3):992–997

    Article  CAS  Google Scholar 

  23. Kim H-J, Choi H-B, Jang J-P, Baek I-C, Choi E-J, Park M, Kim T-G, Oh S-T (2014) HLA-Cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean colorectal cancer patients. Int J Surg 12(8):815–820

    Article  PubMed  Google Scholar 

  24. Barani S, Khademi B, Ashouri E, Ghaderi A (2018) KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with the risk of head and neck squamous cell carcinoma in Iranians. Hum Immunol. https://doi.org/10.1016/j.humimm.2018.01.012

    Article  PubMed  Google Scholar 

  25. Janakiram NB, Rao CV (2014) The role of inflammation in colon cancer. Inflamm Cancer. https://doi.org/10.1007/978-3-0348-0837-8_2

    Article  Google Scholar 

  26. Hagemann T, Balkwill F, Lawrence T (2007) Inflammation and cancer: a double-edged sword. Cancer Cell 12(4):300–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Momot T, Koch S, Hunzelmann N, Krieg T, Ulbricht K, Schmidt R, Witte T (2004) Association of killer cell immunoglobulin-like receptors with scleroderma. Arthritis Rheumatol 50(5):1561–1565

    Article  CAS  Google Scholar 

  28. Ashouri E, Dabbaghmanesh MH, Rowhanirad S, Bakhshayeshkaram M, Omrani GR, Ghaderi A (2012) Activating KIR2DS5 receptor is a risk for thyroid cancer. Hum Immunol 73(10):1017–1022

    Article  CAS  PubMed  Google Scholar 

  29. Carrington M, Wang S, Martin MP, Gao X, Schiffman M, Cheng J, Herrero R, Rodriguez AC, Kurman R, Mortel R (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med 201(7):1069–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by a grant from (Grant No: 93-7202) Shiraz University of Medical Sciences. We thank those who helped us to collect the samples. This study was part of an MSc dissertation in Shiraz Institute for Cancer Research.

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Authors and Affiliations

  1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Shaghik Barani & Abbas Ghaderi

  2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Elham Jamali, Fahimeh Yousefinejad & Abbas Ghaderi

  3. Department of Urology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Ariafar

  4. Hepatitis Research Center, Lorestan University of Medical Sciences, Khoramabad, Iran

    Ghoalm Reza Talei

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  1. Elham Jamali
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  2. Shaghik Barani
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  3. Fahimeh Yousefinejad
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  4. Ali Ariafar
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  5. Ghoalm Reza Talei
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  6. Abbas Ghaderi
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Correspondence to Abbas Ghaderi.

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Jamali, E., Barani, S., Yousefinejad, F. et al. KIRs gene content diversity in Iranians with urothelial bladder cancer. Mol Biol Rep 45, 713–719 (2018). https://doi.org/10.1007/s11033-018-4221-9

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  • DOI: https://doi.org/10.1007/s11033-018-4221-9

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