乳腺癌组织lncRNA CASC2、miR-532-3p表达水平与患者术后5年内生存的相关性

Correlation between the expression of lncRNA CASC2,miR-532-3p in breast cancer tissues and the survival of patients within 5 years after surgery

目的探究乳腺癌(BC)组织长链非编码RNA癌易感性候选基因2(lncRNA CASC2)、微小RNA-532-3p(miR-532-3p)表达与患者术后5年内生存的相关性。方法选择2015年1月—2018年6月大同市第五人民医院普通外科收治BC患者127例,术中收集BC组织及癌旁正常组织,荧光定量PCR法检测BC组织和癌旁正常组织中lncRNA CASC2、miR-532-3p表达;对BC患者术后进行为期5年的随访,记录患者5年内生存和死亡情况。比较癌旁正常组织和BC组织lncRNA CASC2及miR-532-3p表达,BC组织中lncRNA CASC2和miR-532-3p表达在不同临床病理特征中的差异,生存组和死亡组临床病理特征和BC组织中lncRNA CASC2及miR-532-3p表达的差异。分析BC组织lncRNA CASC2、miR-532-3p表达的相关性;BC组织中lncRNA CASC2和miR-532-3p表达与术后5年内生存的关系;影响BC患者术后5年内生存的因素;lncRNA CASC2、miR-532-3p对BC患者术后5年内生存的预测价值。结果BC组织中lncRNA CASC2表达水平低于癌旁正常组织,miR-532-3p表达水平高于癌旁正常组织(t/P=38.239/<0.001,49.406/<0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例lncRNA CASC2低表达组高于高表达组,而miR-532-3p低表达组低于高表达组(lncRNA CASC2:χ^(2)/P=17.361/<0.001、17.052/<0.001、14.694/<0.001、13.173/<0.001;miR-532-3p:χ^(2)/P=10.733/0.001、9.813/0.002、10.134/0.001、7.444/0.006);127例BC患者术后随访5年,生存99例(生存组),死亡28例(死亡组),肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例及miR-532-3p表达水平死亡组高于生存组,而lncRNA CASC2表达水平死亡组低于生存组[χ^(2)(t)/P=5.211/0.022、27.149/<0.001、27.990/<0.001、4.590/0.032、19.155/<0.001、10.818/<0.001];BC组织中lncRNA CASC2与miR-532-3p表达呈负相关(r/P=-0.561/<0.001);lncRNA CASC2高表达组BC患者术后5年内总生存率为89.23%(58/65),高于lncRNA CASC2低表达组66.13%(41/62)(χ^(2)/P=9.854/0.002);miR-532-3p高表达组BC患者术后5年内总生存率为65.57%(40/61),低于miR-532-3p低表达组89.39%(59/66)(χ^(2)/P=10.466/0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、有淋巴结转移、lncRNA CASC2低表达、miR-532-3p高表达均是影响BC患者术后5年内生存的独立危险因素[HR(95%CI)=2.255(1.192~4.263)、2.143(1.252~3.666)、3.089(1.386~6.887)、2.219(1.223~4.026)、2.606(1.174~5.788)、2.855(1.592~5.120)];lncRNA CASC2、miR-532-3p及二者联合预测BC患者术后5年内生存的AUC分别为0.840、0.852、0.908,二者联合预测的AUC大于lncRNA CASC2、miR-532-3p各自单独预测的AUC(Z/P=2.246/0.025、2.033/0.042)。结论BC组织中lncRNA CASC2表达下调,miR-532-3p表达上调,且术后5年内死亡的BC患者较存活患者变化更显著,二者表达与临床病理特征相关,对预测BC患者术后5年内生存情况价值较高。

Objective To explore the correlation between the expression of long non-coding RNA cancer susceptibility candidate 2(lncRNA CASC2),microRNA-532-3p(miR-532-3p)in breast cancer(BC)tissue and the survival of patients within 5 years after surgery.Methods A total of 127 BC patients admitted to Department of General Surgery,the Fifth People's Hospital of Datong City from January 2015 to June 2018 were selected,BC tissues and para-cancer normal tissues were collected during the operation,and the expressions of lncRNA CASC2 and miR-532-3p in BC tissues and para-cancer normal tissues were detected by fluorescence quantitative PCR;the BC patients were followed up for 5 years after surgery,the survival and death of the patients within 5 years were recorded.The expressions of lncRNA CASC2 and miR-532-3p in para-cancer normal tissues and BC tissues,the expression differences of lncRNA CASC2 and miR-532-3p in BC tissues in different clinicopathological characteristics,the clinicopathological characteristics and the expressions of lncRNA CASC2 and miR-532-3p in BC tissues of survival group and death group were compared.Analyze the correlation between the expression of lncRNA CASC2 and miR-532-3p in BC tissue,the relationship between the expression of lncRNA CASC2 and miR-532-3p in BC tissue and postoperative 5-year survival,the factors affecting postoperative 5-year survival of BC patients,and the predictive value of lncRNA CASC2 and miR-532-3p for postoperative 5-year survival of BC patients.Results The expression level of lncRNA CASC2 in BC tissues was significantly lower than that in para-cancer normal tissues,and the expression level of miR-532-3p in BC tissues was significantly higher than that in para-cancer normal tissues(t/P=38.239/<0.001,49.406/<0.001).The proportion of patients with tumor diameter≥2 cm,TNM stageⅢ,low differentiation of tumors and lymph node metastasis in lncRNA CASC2 low expression group were higher than in the high expression group,while the miR-532-3p low expression group was lower than that in the high expression group(lncRNA CASC2:χ^(2)/P=17.361/<0.001,17.052/<0.001,14.694/<0.001,13.173/<0.001,miR-532-3p:χ^(2)/P=10.733/0.001,9.813/0.002,10.134/0.001,7.444/0.006).127 BC patients were followed up for 5 years after surgery,without loss of follow-up,99 cases survived(survival group),28 cases died(death group).The proportion of patients with tumor diameter≥2 cm,TNM stageⅢ,low differentiation of tumors,lymph node metastasis and miR-532-3p expression level in the death group were higher than in the survival group,while the lncRNA CASC2 expression level in the death group was lower than in the survival group[χ^(2)(t)/P=5.211/0.022,27.149/<0.001,27.990/<0.001,4.590/0.032,19.155/<0.001,10.818/<0.001].LncRNA CASC2 was negatively correlated with miR-532-3p expression in BC tissues(r/P=-0.561/<0.001).The 5-year overall survival rate of BC patients after surgery in the lncRNA CASC2 high expression group was 89.23%(58/65)higher than that in the lncRNA CASC2 low expression group 66.13%(41/62)(χ^(2)/P=9.854/0.002);the 5-year overall survival rate of BC patients after surgery in the miR-532-3p high expression group was 65.57%(40/61)lower than that in the miR-532-3p low expression group 89.39%(59/66)(χ^(2)/P=10.466/0.001).Tumor diameter≥2 cm,TNM stageⅢ,low differentiation of tumors,lymph node metastasis,lncRNA CASC2 low expression,and miR-532-3p high expression were all independent risk factors affecting the survival of BC patients within 5 years after surgery[HR(95%CI)=2.255(1.192-4.263),2.143(1.252-3.666),3.089(1.386-6.887),2.219(1.223-4.026),2.606(1.174-5.788),2.855(1.592-5.120)].The area under curve(AUC)of lncRNA CASC2,miR-532-3p,their combined in predicting postoperative 5-year survival of BC patients was 0.840,0.852 and 0.908,respectively,AUC predicted by the combination of the two methods was higher than that predicted by lncRNA CASC2 and miR-532-3p separately(Z/P=2.246/0.025,2.033/0.042).Conclusion The expression of lncRNA CASC2 is down-regulated and the expression of miR-532-3p is up-regulated in BC tissues,and the changes in BC patients who died within 5 years after surgery are more significant than those who survived.The expressions of both are correlated with clinicopathological characteristics,and are of high value in predicting the survival of BC patients within 5 years after surgery.