细胞周期蛋白D1、Aurora激酶A、成纤维生长因子受体2基因多态性与乳腺癌临床病理参数和预后的相关性

Correlation analysis of Cyclin D1,Aurora kinase-A,Fibroblast growth factor receptor2 gene single nucleotide polymorphism with pathological indicators and prognosis of breast cancer

目的探讨乳腺癌细胞周期蛋白D1(CCND1)、Aurora激酶A(AURKA)及成纤维生长因子受体2(FGFR2)基因单核苷酸多态性(SNP)存在和频率及与临床病理和预后的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测新疆医科大学附属肿瘤医院自2014年4月至2019年4月5年间顺序收治的192例女性乳腺癌患者外周血肿瘤增殖相关基因CCND1、AURKA、FGFR2多态性,用χ2检验及非条件的Logistic回归分析计算优势比(OR)及其95%可信区间(CI)评估3种基因SNP与临床病理指标及预后的关系,明确与临床病理及预后因素相关的SNP。结果基因型分析结果表明,CCND1基因G870A位点GG、AG、AA基因型在乳腺癌中的分布频率分别为18.8%(36/192),52.1%(100/192),29.2%(56/192)。G和A等位基因频率分别为44.8%和55.2%。AURKA基因TT、TA、AA基因型在乳腺癌中的分布频率分别为39.6%(76/192)、40.6%(78/192)、19.8%(38/192)。T和A等位基因频率分别为59.9%和40.1%。FGFR2基因SNP位点rs2981582 CC、CT、TT基因型在乳腺癌中的分布频率分别为25.0%(48/192),59.4%(114/192),15.6%(30/192)。C和T等位基因频率分别为54.7%和45.3%。CCND1 SNP与乳腺癌临床病理指标及预后无明显相关(χ2=3.882、0.051、4.006、1.311、0.693、2.035,P>0.05);AURKA SNP与直径、分期和淋巴结转移相关(χ2=0.586、6.402、8.251,P<0.05),FGFR2 SNP与淋巴结转移、ER、PR、Her-2相关(χ2=7.586、6.466、7.631、6.752,P<0.05)。AURKA及FGFR2 SNP与乳腺癌预后明显相关(χ2=9.493、7.017,P<0.05),携带AURKA TT基因型患者预后较差,OR值为3.007(95%CI=1.477~6.120,P<0.01),差异有统计学意义,携带TT或TA基因型患者预后较差,OR值为2.385(95%CI=1.267~4.488,P<0.05),差异有统计学意义。携带FGFR2 TT基因型患者预后较差,OR值为4.00(95%CI=1.388~11.53,P<0.05),差异有统计学意义。结论 AURKA TT/TA、FGFR2 TT可能是乳腺癌预后不良基因型,AURKA及FGFR2 SNPs可作为判断乳腺癌预后的生物标志物。

Objective:To investigate the relationship between the presence and frequency of single nucleotide polymorphisms(SNPs)of cyclin D1(CCND1),Aurora kinase A(AURKA)and fibroblast growth factor receptor 2(FGFR2)genes and clinicopathological and prognostic factors in breast cancer.investigate the presence and frequency of SNPs in CCND,AURKA and FGFR2 genes in breast cancer and their relationship with clinical pathology and prognosis.Methods:Restriction fragment length polymorphism(PCR-RFLP)method was used to detect the polymorphism of CCND1,AURKA,FGFR2 of peripheral blood of 192 female breast cancer patients treated in our hospital from April 2014 to April 2019.Odds ratio(OR)and 95%confidence interval(CI)were calculated by chi square test and unconditional logistic regression analysis to evaluate the relationship between SNPs of three genes and clinicopathological indexes and prognosis.Results:Genotype analysis showed that the frequencies of GG,AG and AA genotypes at G870A of CCND1 were 18.8%(36/192),52.1%(100/192)and 29.2%(56/192),respectively.The frequencies of G and A alleles were 44.8%and 55.2%,respectively.The frequencies of AURKA TT,TA and AA genotypes were 39.6%(76/192),40.6%(78/192)and 19.8%(38/192),respectively.The frequencies of T and A alleles were 59.9%and 40.1%,respectively.The frequencies of rs2981582 CC,CT and TT genotypes in breast cancer were 25.0%(48/192),59.4%(114/192)and 15.6%(30/192),respectively.The frequencies of C and T alleles were 54.7%and 45.3%respectively.CCND1 SNP was not correlated with clinicopathological parameters and prognosis of breast cancer(χ2=3.882,0.051,4.006,1.311,0.693,2.035,P>0.05);AURKA SNP was associated with diameter,stage and lymph node metastasis(χ2=0.586,6.402,8.251,P<0.05);FGFR2 SNP was associated with lymph node metastasis,ER,PR,Her-2(χ2=7.586,6.466,7.631,6.752,P<0.05).AURKA and FGFR2 SNP were correlated with the prognosis of breast cancer(χ2=9.493,7.017,P<0.05).The prognosis of patients with AURKA TT genotype was poor,or value was 3.007(95%CI=1.477-6.120,P<0.01).The prognosis of patients with TT or TA genotype was poor,or value was 2.385(95%CI=1.267-4.488,P<0.05).Patients with FGFR2 TT genotype had poor prognosis,or value was 4.00(95%CI=1.388-11.53,P<0.05).Conclusion:TT or TA AURKA genotype,TT FGFR2 genotype may be risk gene for breast cancer,AURKA and FGFR2 SNPs can be used as biomarkers to judge the prognosis of breast cancer and guide the clinical diagnosis and treatment of breast cancer.