分泌型卷曲相关蛋白4、微小RNA-126-5p在三阴乳腺癌组织中表达及与临床病理特征的关系

Expression of secreted frizzled-related protein 4 and miR-126-5p in triple-negative breast cancer tissues and their relationship with clinicopathological characteristics

目的探究分泌型卷曲相关蛋白4(SFRP4)、微小RNA-126-5p在三阴乳腺癌组织中表达及与临床病理特征的关系。方法选取2014年10月至2016年10月在沧州市人民医院接受手术切除治疗的三阴乳腺癌病人78例作为研究对象,取其癌组织及癌旁组织(距离肿瘤边缘5 cm),以SP免疫组化法检测SFRP4表达情况,以RT-qPCR分析法检测miR-126-5p水平。收集病人资料,分析SFRP4、miR-126-5p表达与三阴乳腺癌病人临床病理特征的关系。以Spearman等级相关性分析SFRP4、miR-126-5p表达的相关性。绘制K-M生存曲线分析病人生存状态,行Cox多因素分析影响三阴乳腺癌病人预后的因素。结果三阴乳腺癌组织中SFRP4阳性率[53.85%(42/78)]明显高于癌旁组织[37.18%(29/78)](P<0.05),miR-126-5p表达0.78±0.21明显低于癌旁组织1.00±0.00(P<0.05)。对纳入病人进行临床病理特征分析,结果显示,SFRP4表达与淋巴结转移[78.13%(25/32)比36.96%(17/46)]、肿瘤浸润程度[65.12%(28/43)比22.86%(8/35)]、细胞增殖抗原Ki-67表达[83.33%(20/24)比40.74%(22/54)]有关(P<0.05),而与年龄、肿瘤大小、TNM分期、组织学分级无关(P>0.05)。miR-126-5p与淋巴结转移[81.25%(26/32)比30.43%(14/46)]、Ki-67表达[70.83%(17/24)比42.59%(23/54)]有关(P<0.05),而与年龄、肿瘤大小、TNM分期、组织学分级及肿瘤浸润程度无关(P>0.05)。行Spearson相关性分析,结果显示,SFRP4、miR-126-5p在三阴乳腺癌组织中具有相关性(P<0.05)。对病人进行为期5年的随访,生存63例,死亡15例。miR-126-5p低表达组病人生存28例,死亡12例,miR-126-5p高表达组生存35例,死亡3例,组间比较差异有统计学意义(P<0.05);SFRP4阳性组病人生存29例,死亡13例;SFRP4阴性组病人生存34例,死亡2例,组间比较差异有统计学意义(P<0.05)。行多因素Cox分析,结果显示,有淋巴结转移、Ki-67阳性、miR-126-5p低表达、SFRP4阳性为影响三阴乳腺癌病人预后的独立危险因素(P<0.05)。结论三阴乳腺癌组织中miR-126-5p呈低表达,SFRP4阳性率高,两者表达具有相关性,可作为预测三阴乳腺癌病人预后的重要指标。

Objective To explore the expression of secreted frizzled-related protein 4(SFRP4)and miR-126-5p in triple-negative breast cancer tissues and their relationship with clinicopathological characteristics.Methods Seventy-eight patients with triple-negative breast cancer who underwent surgical resection in our hospital were selected as the research objects.The cancer tissues and adjacent tissues(5 cm from the tumor edge)were taken,SP immunohistochemistry was used to detect the expression of SFRP4,and RT-qPCR analysis method was used to detect the level of miR-126-5p.The data of patients were collected,and the relationship between the expression of SFRP4,miR-126-5p and the clinicopathological characteristics of triple-negative breast cancer patients was analyzed.Spearman rank correlation was used to analyze the correlation between SFRP4 and miR-126-5p expression.K-M survival curve was plotted to analyze the survival status of patients,Cox multivariate analysis was performed to analyze the factors affecting the prognosis of patients with triple-negative breast cancer.Results The positive rate of SFRP4 in triple-negative breast cancer tissues[53.85%(42/78)]was significantly higher than that in adjacent tissues[37.18%(29/78)](P<0.05),and the expression of miR-126-5p(0.78±0.21)was significantly lower than that in adjacent tissues(1.00±0.00)(P<0.05).The clinical pathological characteristics of the included patients were analyzed,and the results showed that the expression of SFRP4 was related to lymph node metastasis[78.13%(25/32)vs.36.96%(17/46)],tumor invasion[65.12%(28/43)vs.22.86%(8/35)]and Ki-67 expression[83.33%(20/24)vs.40.74%(22/54)](P<0.05),but not related to age,tumor size,TNM stage and histological grade(P>0.05).MiR-126-5p was related to lymph node metastasis[81.25%(26/32)vs.30.43%(14/46)]and Ki-67 expression[70.83%(17/24)vs.42.59%(23/54)](P<0.05),but not related to age,tumor size,TNM stage,histological grade,and tumor invasion(P>0.05).Spearson correlation analysis was performed,and the results showed that SFRP4 and miR-126-5p were correlated in triple-negative breast cancer tissues(P<0.05).The patients were followed up for 5 years,63 cases survived and 15 died.In the miR-126-5p low expression group,28 patients survived and 12 died,while in the miR-126-5p high expression group,35 patients survived and 3 died,and the difference between the two groups was statistically significant(P<0.05);in the SFRP4 positive group,29 patients survived and 13 died,while in the SFRP4 negative group,34 patients survived and 2 died,and the difference between the two groups was statistically significant(P<0.05).Multivariate Cox analysis showed that lymph node metastasis,Ki-67 positive,low expression of miR-126-5p and positive SFRP4 were independent risk factors affecting the prognosis of patients with triple-negative breast cancer(P<0.05).Conclusion The expression of miR-126-5p in triple-negative breast cancer tissue is low,and the positive rate of SFRP4 is high.Their expression is correlated and can be used as an important indicator for predicting the prognosis of patients with triple-negative breast cancer.