RegⅣ在不同分子分型乳腺癌中的表达及意义

Expression and significance of RegⅣin breast cancer and its specific molecular subtypes

目的探讨再生胰岛衍生家族成员Ⅳ(RegⅣ)在不同分子分型乳腺癌中的表达及临床意义。方法选取徐州医科大学附属连云港第一人民医院2017年1月-2019年5月间收集的140例乳腺癌手术切除标本,其中腺腔A型(LA)30例、腺腔B型(LB)50例、人表皮生长因子受体-2(HER-2)过表达型(HER-2+)30例和三阴性乳腺癌(TNBC)30例;以其中75例癌旁的正常乳腺组织作为对照。采用EnVison免疫组化染色和实时荧光定量PCR法检测各组织RegⅣ蛋白和mRNA的表达,分析不同分子分型患者RegⅣ表达的差异及其与乳腺癌相关标志物及临床病理特征间的关系。利用Kaplan-Meier Plotter数据库分析乳腺癌患者RegⅣmRNA表达与预后的关系。结果(1)RegⅣ蛋白在癌组织中的阳性率高于正常组织(49.29%vs.25.33%,χ^2=11.589,P<0.01),非TNBC型中的阳性率高于TNBC型(56.36%vs.23.33%,χ^2=10.289,P<0.01)。(2)RegⅣmRNA在乳腺癌中的表达高于正常乳腺组织(P<0.05),非TNBC组高于正常组和TNBC组,正常乳腺和TNBC组间差异无统计学意义。(3)在雌激素受体(ER)+、孕激素受体(PR)+、HER-2+组中的RegⅣmRNA表达水平明显高于各自阴性表达组(P<0.01),但在EGFR阳性组和阴性组及Ki-67高表达和低表达组比较差异均无统计学意义。(4)年龄在40岁以上、肿瘤直径≤2 cm、TNM分期为Ⅰ~Ⅱ期患者的RegⅣmRNA表达水平较高。(5)Kaplan-Meier Plotter数据库显示乳腺癌RegⅣmRNA高表达患者无复发生存期、总生存期、无远处复发生存期和复发后生存期较低表达者明显延长,预后较好。结论RegⅣ在乳腺癌,尤其非TNBC型的发生发展中可能发挥作用,且与患者的预后相关,有望为乳腺癌的治疗提供潜在的治疗靶点。

ObjectiveTo investigate the expression of clinical significance of regenerating islet-dered family member(Reg)Ⅳin breast cancer and its specific molecular subtypes.MethodsA total of 140 surgical resection specimens ofmalignant breast cancer were collected at the First People′s Hospital of Lianyungang affiliated to Xuzhou Medical Universityfrom January 2017 to May 2019,including 30 cases of luminal A(LA),50 cases of luminal B(LB),30 cases of epidermalgrowth factor receptor 2(HER-2)overexpression(HER-2+)and 30 cases of triple negative breast cancer(TNBC).Seventysamples of normal breast tissues were used as the control group.En Vison immunohistochemistry was used to detect theexpression of RegⅣprotein.Real-time quantitative PCR was used to analyze RegⅣm RNA.The relationship between theexpressions of RegⅣin patients with different molecular subtypes and clinical pathological features was analyzede.Kaplan-Meier Plotter database was used to analyze the relationship between the expression of RegⅣm RNA and prognosis in breastcancer patients.Results(1)The positive rate of RegⅣprotein was higher in malignant breast cancer compared with thatof normal breast tissues(49.29%vs.25.33%,χ^2=11.589,P<0.01),and which was higher in non-TNBC than that in TNBC(56.36%vs.23.33%,χ^2=10.289,P<0.01).(2)The expression of RegⅣm RNA was higher in malignant breast cancer thanthat in normal breast tissues.Among different molecular types,the expression of non-TNBC group was higher than that of thenormal and TNBC groups.There was no significant difference in the expression of RegⅣm RNA between the normal andTNBC groups.(3)The expressions of RegⅣmRNA were up-regulated in positive ER,PR and HER-2 groups than those oftheir negative groups(P<0.05).There were no significant differences in expressions of RegⅣmRNA between EGFRpositive group and EGFR negative group,and between high expression of Ki-67 group and lower expression of Ki-67 group.(4)The expression of RegⅣm RNA was significantly associated with patient age,tumor size,TNM stage and prognosis(P<0.05),but it was not significantly correlated with lymph node metastasis,histological grade and tumor site.(5)Kaplan-MeierPlotter database showed that patients with high expression of RegⅣm RNA in breast cancer had significantly higher RFS,OS,DMFS,and PPS.ConclusionResults demonstrate that RegⅣmay play an important role in malignant breast cancer,especially in non TNBC.The expression of RegⅣmay be related with the prognosis of breast cancer patients,and it isexpected to provide potential therapeutic targets for the treatment of breast cancer.