微管相关蛋白9编码基因rs1058992位点多态性与EBV相关肿瘤易感性
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摘要
目的探讨微管相关蛋白9(MAP9)编码基因rs1058992位点多态性与EB病毒(EBV)相关肿瘤的关系。方法采用飞行时间质谱技术,检测3种EBV相关肿瘤(胃癌、鼻咽癌、淋巴瘤)与正常人外周血MAP9基因rs1058992位点基因型,比较肿瘤病人与正常人、EBV阳性肿瘤与EBV阴性肿瘤间基因型与等位基因频率的差异。结果 EBV相关胃癌(EBVaGC)与EBV阴性胃癌(EBVnGC)MAP9基因rs1058992位点TT、CT、CC基因型分布及T、C等位基因频率比较差异均有显著性(χ2=7.687、6.154,P<0.05);EBVaGC与正常对照组C等位基因频率比较差异有显著性(χ2=4.442,P<0.05);EBVnGC与正常对照组比较,TT、CT、CC基因型分布及T、C等位基因频率差异均无统计学意义(P>0.05)。EBV阳性鼻咽癌与EBV阴性鼻咽癌、正常对照组比较,TT、CT、CC基因型分布及T、C等位基因频率差异均无显著性(P>0.05)。EBV阳性淋巴瘤与EBV阴性淋巴瘤、正常对照组间比较,TT、CT、CC基因型分布及T、C等位基因频率差异均无显著性(P>0.05)。结论 MAP9基因rs1058992位点多态性和等位基因均与EBVaGC易感性有关,C等位基因可能是EBVaGC的危险因素。
Objective To investigate the association of microtubule-associated protein 9(MAP9)rs1058992 polymorphism with Epstein-Barr virus(EBV)-associated tumors. Methods Time-of-flight mass spectrometry was used to determine the genotype of MAP9 gene rs1058992 in the patients with one of the three EBV-associated tumors(gastric cancer,nasopharyngeal carcinoma,and lymphoma)and peripheral blood samples of normal subjects.Genotype and allele frequencies were compared between tumor patients and normal subjects and between EBV-positive tumors and EBV-negative tumors. Results There were significant differences in the distribution of TT,CT,and CC genotypes of MAP9 rs1058992 and the frequencies of T and C alleles between the EBV-associated gastric cancer(EBVaGC)group and the EBV-negative gastric cancer(EBVnGC)group(χ2=7.687 and 6.154,P<0.05).There was a significant difference in the frequency of C allele between the EBVaGC group and the normal control group(χ2=4.442,P<0.05).There were no significant differences between the EBVnGC group and the normal control group in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles(P>0.05).There were no significant differences in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles between the EBV-positive nasopharyngeal carcinoma group and the EBV-negative nasopharyngeal carcinoma group/normal control group(P>0.05).There were also no significant differences in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles between the EBV-positive lymphoma group and the EBV-negative lymphoma group/normal control group(P>0.05). Conclusion MAP9 rs1058992 polymorphism and allele are associated with the susceptibility to EBVaGC,and the C allele may be a risk factor for EBVaGC.
Objective To investigate the association of microtubule-associated protein 9(MAP9)rs1058992 polymorphism with Epstein-Barr virus(EBV)-associated tumors. Methods Time-of-flight mass spectrometry was used to determine the genotype of MAP9 gene rs1058992 in the patients with one of the three EBV-associated tumors(gastric cancer,nasopharyngeal carcinoma,and lymphoma)and peripheral blood samples of normal subjects.Genotype and allele frequencies were compared between tumor patients and normal subjects and between EBV-positive tumors and EBV-negative tumors. Results There were significant differences in the distribution of TT,CT,and CC genotypes of MAP9 rs1058992 and the frequencies of T and C alleles between the EBV-associated gastric cancer(EBVaGC)group and the EBV-negative gastric cancer(EBVnGC)group(χ2=7.687 and 6.154,P<0.05).There was a significant difference in the frequency of C allele between the EBVaGC group and the normal control group(χ2=4.442,P<0.05).There were no significant differences between the EBVnGC group and the normal control group in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles(P>0.05).There were no significant differences in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles between the EBV-positive nasopharyngeal carcinoma group and the EBV-negative nasopharyngeal carcinoma group/normal control group(P>0.05).There were also no significant differences in the distribution of TT,CT,and CC genotypes and the frequencies of T and C alleles between the EBV-positive lymphoma group and the EBV-negative lymphoma group/normal control group(P>0.05). Conclusion MAP9 rs1058992 polymorphism and allele are associated with the susceptibility to EBVaGC,and the C allele may be a risk factor for EBVaGC.
引文
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[21]BASBOUS J,KNANI D,BONNEAUD N,et al.Induction of ASAP(MAP9)contributes to p53stabilization in response to DNA damage[J].Cell Cycle,2012,11(12):2380-2390.
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[23]YOUNG L S,DAWSON C W,CLARK D,et al.Epstein-Barr virus gene expression in nasopharyngeal carcinoma[J].Journal of General Virology,1988,69(5):1051-1065.
[24]GONG L P,CHEN J N,XIAO L,et al.The implication of tumor infiltrating lymphocytes in Epstein-Barr virus-associated gastric carcinoma[J].Human Pathology,2018,15:S0046-8177(18)30426-X.
[25]VRZALIKOVA K,IBRAHIM M,NAGY E,et al.Co-expression of the Epstein-Barr virus-encoded latent membrane proteins and the pathogenesis of classic hodgkin lymphoma[J].Cancers,2018,10(9):E285.
[26]LO A K,LUNG R W,DAWSON C W,et al.Activation of sterol regulatory element-binding protein 1(SREBP1)-mediated lipogenesis by the Epstein-Barr virus-encoded latent membrane protein 1(LMP1)promotes cell proliferation and progression of nasopharyngeal carcinoma[J].Journal of Pathology,2018,246(2):180-190.
[27]TSAO S W,TSANG C M,PANG P S,et al.The biology of EBV infection in human epithelial cells[J].Seminars in Cancer Biology,2012,22(2):137-143.
[28]CHEN X Z,CHEN H D,CASTRO F A,et al.Epstein-Barr virus infection and gastric cancer:a systematic review[J].Medicine,2015,94(20):e792.
[2]WILLIAMS H,CRAWFORD D H.Epstein-Barr virus:the impact of scientific advances on clinical practice[J].Blood,2006,107(3):862-869.
[3]TOKUNAGA M,LAND C E,UEMURA Y,et al.EpsteinBarr virus in gastric carcinoma[J].American Journal of Pathology,1993,143(5):1250-1254.
[4]OSATO T,IMAI S.Epstein-Barr virus and gastric carcinoma[J].Seminars in Cancer Biology,1996,7(4):175-182.
[5]MOHAN R,JOHN A.Microtubule-associated proteins as direct crosslinkers of actin filaments and microtubules[J].IUBMB Life,2015,67(6):395-403.
[6]RAMKUMAR A,JONG B Y,ORI-MCKENNEY K M.ReMAPping the microtubule landscape:how phosphorylation dictates the activities of microtubule-associated proteins[J].Developmental Dynamics,2018,247(1,SI):138-155.
[7]TOKURAKU K,KATSUKI M,MATUI T,et al.Microtubule-binding property of microtubule-associated protein 2differs from that of microtubule-associated protein 4and tau[J].European Journal of Biochemistry,1999,264(3):996-1001.
[8]冯佳韵.微管相关蛋白2预测恶性黑素瘤侵袭性的临床研究[D].大连:大连医科大学,2015.
[9]SAFFIN J M,VENOUX M,PRIGENT C,et al.ASAP,a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis[J].Proceedings of the National Academy of Sciences of the United States of America,2005,102(32):11302-11307.
[10]VENOUX M,BASBOUS J,BERTHENET C,et al.ASAP is a novel substrate of the oncogenic mitotic kinase Aurora-A:phosphorylation on Ser625is essential to spindle formation and mitosis[J].Human Molecular Genetics,2008,17(2):215-224.
[11]EOT-HOULLIER G,VENOUX M,VIDAL-EYCHENIE SA,et al.Plk1regulates both ASAP localization and its role in spindle Pole integrity[J].Journal of Biological Chemistry,2010,285(38):29556-29568.
[12]BROOKES A J.The essence of SNPs[J].Gene,1999,234(2):177-186.
[13]WANG Fang,SUN Guoping,ZOU Yanfeng,et al.Quantitative assessment of the association between miR-196a2rs11614913polymorphism and gastrointestinal cancer risk[J].Molecular Biology Reports,2013,40(1):109-116.
[14]GONZALEZ-HORMAZABAL P,ROMERO S,MUSLEH MA,et al.IL-8-251T>A(rs4073)polymorphism is associated with prognosis in gastric cancer patients[J].Anticancer Research,2018,38(10):5703-5708.
[15]LIU Ying,YANG Wenjun,PAN Yaqi,et al.Genome-wide analysis of Epstein-Barr virus(EBV)isolated from EBV-associated gastric carcinoma(EBVaGC)[J].Oncotarget,2016,7(4):4903-4914.
[16]SONG Y,LIU S,ZHAO Z,et al.Relationship between PPP1R15Agene polymorphism(rs611251)and Epstein-Barr virus-associated tumors[J].Acta Virologica,2017,61(4):445-452.
[17]LOPES L F,BACCHI M M,ELGUI-DE-OLIVEIRA D,et al.Epstein-Barr virus infection and gastric carcinoma in Sao Paulo State,Brazil[J].Brazilian Journal of Medical and Biological Research,2004,37(11):1707-1712.
[18]TOKUNAGA M,LAND C E,UEMURA Y,et al.EpsteinBarr virus in gastric carcinoma[J].The American Journal of Pathology,1993,143(5):1250-1254.
[19]冯思坛,施鑫.微管相关蛋白与肿瘤关系的研究进展[J].医学研究生学报,2013,26(8):878-881.
[20]ROUQUIER S,PILLAIRE M J,CAZAUX C A.Expression of the microtubule-associated protein MAP9/ASAP and its partners AURKA and PLK1in colorectal and breast cancers[J].Disease Markers,2014,2014:798170.doi:10.1155/2014/798170.
[21]BASBOUS J,KNANI D,BONNEAUD N,et al.Induction of ASAP(MAP9)contributes to p53stabilization in response to DNA damage[J].Cell Cycle,2012,11(12):2380-2390.
[22]KANAKRY J A,AMBINDER R F.EBV-related lymphomas:new approaches to treatment[J].Current Treatment Options in Oncology,2013,14(2):224-236.
[23]YOUNG L S,DAWSON C W,CLARK D,et al.Epstein-Barr virus gene expression in nasopharyngeal carcinoma[J].Journal of General Virology,1988,69(5):1051-1065.
[24]GONG L P,CHEN J N,XIAO L,et al.The implication of tumor infiltrating lymphocytes in Epstein-Barr virus-associated gastric carcinoma[J].Human Pathology,2018,15:S0046-8177(18)30426-X.
[25]VRZALIKOVA K,IBRAHIM M,NAGY E,et al.Co-expression of the Epstein-Barr virus-encoded latent membrane proteins and the pathogenesis of classic hodgkin lymphoma[J].Cancers,2018,10(9):E285.
[26]LO A K,LUNG R W,DAWSON C W,et al.Activation of sterol regulatory element-binding protein 1(SREBP1)-mediated lipogenesis by the Epstein-Barr virus-encoded latent membrane protein 1(LMP1)promotes cell proliferation and progression of nasopharyngeal carcinoma[J].Journal of Pathology,2018,246(2):180-190.
[27]TSAO S W,TSANG C M,PANG P S,et al.The biology of EBV infection in human epithelial cells[J].Seminars in Cancer Biology,2012,22(2):137-143.
[28]CHEN X Z,CHEN H D,CASTRO F A,et al.Epstein-Barr virus infection and gastric cancer:a systematic review[J].Medicine,2015,94(20):e792.