NME1多态性与非小细胞肺癌易感性的关系分析
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摘要
目的探讨非转移性细胞1基因(NME1)单核苷酸多态性(SNPs)与非小细胞肺癌(NSCLC)易感性的关系。方法收集本院2014年1月至2017年12月经病理确诊的168例NSCLC患者的外周血标本,于Sequenom MassARRAY系统上利用基质辅助激光解吸电离飞行时间质谱法进行NME1多态性位点rs16949649、rs2302254和rs34214448的基因分型,选取184例健康体检者的外周血作对比,采用Hardy-Weinberg平衡分析以上3个SNPs位点的遗传平衡情况,比较NSCLC患者与健康对照以上SNPs基因型和等位基因的分布差异并计算比值比来评价以上SNPs与NSCLC易感性的关系。结果 168例NSCLC患者和184例健康体检者的NME1位点rs16949649、rs2302254和rs34214448基因型的分布符合Hardy-Weinberg平衡。NSCLC组与对照组的rs2302254基因型和等位基因分布差异无统计学意义(P>0.05);rs16949649分布上,NSCLC组CC基因型频率为31.0%,C等位基因频率为53.3%,均高于对照组的20.1%和41.8%,差异有统计学意义(P<0.05);rs34214448分布上,NSCLC组TT基因型频率为17.9%,T等位基因频率为45.2%,高于对照组的9.8%和35.6%,差异有统计学意义(P<0.05)。NME1 rs2302254与NSCLC的发病风险无关(P>0.05);rs16949649分布上,以TT基因型为参照,CC基因型发生NSCLC的风险升高至2.297倍,TC+CC则升高至1.774倍(P<0.05);以T等位基因为参照,C发生NSCLC的风险升高至1.584倍(P<0.05)。rs34214448分布上,以GG基因型为参照,TT基因型发生NSCLC的风险升高至2.572倍,GT+TT则升高至1.666倍(P<0.05);以G等位基因为参照,T发生NSCLC的风险升高至1.500倍(P<0.05)。结论 NME1 rs16949649和rs34214448与NSCLC易感性有关,其中携带突变等位基因的NSCLC发生风险升高,在NSCLC易感人群筛查中有一定价值。
Objective To investigate the association of single nucleotide polymorphisms(SNPs) of non-metastatic cell 1 gene(NME1) with susceptibility to non-small cell lung cancer(NSCLC). Methods From January 2014 to December 2017, peripheral blood samples were collected from 168 cases of NSCLC patients following pathological diagnosis. Using the Sequenom MassARRAY system via matrix assisted laser desorption ionization time-of-flight mass spectrometry, NME1 polymorphisms of rs16949649, rs2302254 and rs34214448 were genotyped. The peripheral blood samples of 184 healthy controls were selected for comparison. The distribution of SNP genotypes and alleles in NSCLC patients and healthy controls were compared and the odds ratio was calculated to evaluate the relationship between SNPs and NSCLC susceptibility. Results The distribution of rs16949649, rs2302254 and rs34214448 in 168 NSCLC patients and 184 healthy subjects was in accordance with Hardy-Weinberg balance. There was no significant difference in genotype and allele distribution of rs2302254 between NSCLC group and control group(P>0.05). Regarding rs16949649 distribution, higher frequencies were observed in NSCLC group rather than control group in terms of CC genotype(31.0% vs. 20.1%) and C allele(53.3% vs. 41.8%). Regarding rs34214448 distribution, higher frequencies were observed in NSCLC group rather than control group in terms of TT genotype(17.9% vs. 9.8%) and T allele(45.2% vs. 35.6%). NME1 rs2302254 was not linked to the risk of NSCLC(P>0.05). For rs16949649, as compared to TT genotype, CC and TC+CC genotype increased the risk of NSCLC to 2.297 and 1.774 folds(P<0.05). When taking T allele as the reference, risk of C for NSCLC increased to 1.584 folds(P<0.05). Likewise, for rs34214448, as compared to GG genotype, TT and GT+TT genotype increased the risk of NSCLC to 2.572 and 1.666 folds(P<0.05). When taking G allele as the reference, risk of T for NSCLC increased to 1.500 folds(P<0.05). Conclusion NME1 rs16949649 and rs34214448 were associated with increased susceptibility to NSCLC, and the risk of NSCLC associated with G allele increases, showing a certain value in the screening of NSCLC susceptible population.
Objective To investigate the association of single nucleotide polymorphisms(SNPs) of non-metastatic cell 1 gene(NME1) with susceptibility to non-small cell lung cancer(NSCLC). Methods From January 2014 to December 2017, peripheral blood samples were collected from 168 cases of NSCLC patients following pathological diagnosis. Using the Sequenom MassARRAY system via matrix assisted laser desorption ionization time-of-flight mass spectrometry, NME1 polymorphisms of rs16949649, rs2302254 and rs34214448 were genotyped. The peripheral blood samples of 184 healthy controls were selected for comparison. The distribution of SNP genotypes and alleles in NSCLC patients and healthy controls were compared and the odds ratio was calculated to evaluate the relationship between SNPs and NSCLC susceptibility. Results The distribution of rs16949649, rs2302254 and rs34214448 in 168 NSCLC patients and 184 healthy subjects was in accordance with Hardy-Weinberg balance. There was no significant difference in genotype and allele distribution of rs2302254 between NSCLC group and control group(P>0.05). Regarding rs16949649 distribution, higher frequencies were observed in NSCLC group rather than control group in terms of CC genotype(31.0% vs. 20.1%) and C allele(53.3% vs. 41.8%). Regarding rs34214448 distribution, higher frequencies were observed in NSCLC group rather than control group in terms of TT genotype(17.9% vs. 9.8%) and T allele(45.2% vs. 35.6%). NME1 rs2302254 was not linked to the risk of NSCLC(P>0.05). For rs16949649, as compared to TT genotype, CC and TC+CC genotype increased the risk of NSCLC to 2.297 and 1.774 folds(P<0.05). When taking T allele as the reference, risk of C for NSCLC increased to 1.584 folds(P<0.05). Likewise, for rs34214448, as compared to GG genotype, TT and GT+TT genotype increased the risk of NSCLC to 2.572 and 1.666 folds(P<0.05). When taking G allele as the reference, risk of T for NSCLC increased to 1.500 folds(P<0.05). Conclusion NME1 rs16949649 and rs34214448 were associated with increased susceptibility to NSCLC, and the risk of NSCLC associated with G allele increases, showing a certain value in the screening of NSCLC susceptible population.
引文
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[19] Khan I,Steeg PS.The relationship of NM23(NME) metastasis suppressor histidine phosphorylation to its nucleoside diphosphate kinase,histidine protein kinase and motility suppression activities [J].Oncotarget,2018,9(12):10185-10202.
[20] 郑海霞,崔永言,申东兰,等.Nm23-H1基因转染对肺癌细胞MMP-9和TIMP-1表达的影响[J].临床肿瘤学杂志,2015,20(2):104-107.
[2] Vasile E,Tibaldi C,Leon GL,et al.Cytochrome P450 1B1(CYP1B1) polymorphisms are associated with clinical outcome of docetaxel in non-small cell lung cancer (NSCLC) patients [J].J Cancer Res Clin Oncol,2015,141(7):1189-1194.
[3] Zeng Y,Zhu J,Qin H,et al.Methylated +322-327 CpG site decreases hOGG1 mRNA expression in non-small cell lung cancer [J].Oncol Rep,2017,38(1):529-537.
[4] Xin C,Legrand AJ,Cunniffe S,et al.Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients [J].Cell Oncol(Dordr),2018,41(5):527-539.
[5] 黄景慧,王庭丰,陈欣.晚期非小细胞肺癌中SOD2基因多态性与含铂方案化疗敏感性的研究[J].临床肿瘤学杂志,2016,21(6):508-513.
[6] Leonard MK,Mccorkle JR,Snyder DE,et al.Identification of a gene expression signature associated with the metastasis suppressor function of NME1:prognostic value in human melanoma [J].Lab Invest,2018,98(3):327-338.
[7] Shi X,Jin H,Peng M,et al.Association between NME1 polymorphisms and cancer susceptibility:A meta-analysis based on 1644 cases and 2038 controls [J].Pathol Res Pract,2018,214(4):467-474.
[8] Li Y,Kang S,Qin JJ,et al.Nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease [J].Gynecol Oncol,2012,126(3):455-459.
[9] Huang XI,Zhao W,Li Y,et al.Association between nm23 gene polymorphisms and the risk of endometriosis [J].Biomed Rep,2015,3(6):874-878.
[10] Iqbal B,Masood A,Lone MM,et al.Polymorphism of metastasis suppressor genes MKK4 and NME1 in Kashmiri metastasis suppressor genes [J].Breast J,2016,22(6):673-677.
[11] Su WM,Chen ZH,Zhang XC,et al.Single nucleotide polymorphisms in VTI1A gene contribute to the susceptibility of Chinese population to non-small cell lung cancer [J].Int J Biol Markers,2015,30(3):286-293.
[12] Ahn MJ,Ahn JS,Park K,et al.A single nucleotide polymorphism in the phospholipase D1 gene is associated with risk of non-small cell lung cancer [J].Int J Biomed Sci,2012,8(2):121-128.
[13] 师少军,张玉.NME1基因多态性与疾病易感性、药物代谢的关联研究进展[J].中国医院药学杂志,2018,38(14):1558-1562.
[14] Kaetzel DM,Leonard MK,Cook GS,et al.Dual functions of NME1 in suppression of cell motility and enhancement of genomic stability in melanoma [J].Naunyn Schmiedebergs Arch Pharmacol,2015,388(2):199-206.
[15] Wang PH,Yi YC,Tsai HT,et al.Significant association of genetic polymorphism of human nonmetastatic clone 23 type 1 gene with an increased risk of endometrial cancer [J].Gynecol Oncol,2010,119(1):70-75.
[16] Li AL,Zhou X,Wang ZN,et al.Associations of non-metastatic cells 1 gene polymorphisms with lymph node metastasis risk of gastric cancer in Northern Chinese population [J].Tumour Biol,2012,33(6):2159-2166.
[17] Hsieh YS,Lee YL,Yang SF,et al.Association of EcoRI polymorphism of the metastasis-suppressor gene NME1 with susceptibility to and severity of non-small cell lung cancer[J].Lung Cancer,2007,58(2):191-195.
[18] 刘亚妮,杨春晓,沈如飞,等.肿瘤转移抑制基因Nm23多态性在湖北汉族肾移植患者中的分布[J].中国医院药学杂志,2015,35(1):1-5.
[19] Khan I,Steeg PS.The relationship of NM23(NME) metastasis suppressor histidine phosphorylation to its nucleoside diphosphate kinase,histidine protein kinase and motility suppression activities [J].Oncotarget,2018,9(12):10185-10202.
[20] 郑海霞,崔永言,申东兰,等.Nm23-H1基因转染对肺癌细胞MMP-9和TIMP-1表达的影响[J].临床肿瘤学杂志,2015,20(2):104-107.