乳腺癌患者血清外泌体lncRNA HOTTIP的表达及临床意义

Expression of Serum Exosomal lncRNA HOTTIP in Breast Cancer Patients and Its Clinical Significance

目的探究血清外泌体lncRNA HOTTIP在乳腺癌(breast cancer,BC)患者中的临床预后价值。方法采用试剂盒提取98例BC患者、50例良性乳腺疾病(benign breast disease,BBD)患者和50例健康人血清中的外泌体;采用RT-qPCR检测血清外泌体中HOTTIP的表达水平,进一步分析HOTTIP表达与患者临床病理学特征及总生存期的关系。结果BC患者血清外泌体中lncRNA HOTTIP的表达水平明显高于BBD患者(t=8.790,P<0.001)和正常健康人(t=11.540,P<0.001),且手术后BC患者血清外泌体中的HOTTIP水平显著降低(t=14.570,P<0.001)。临床病理分析显示,高血清外泌体HOTTIP水平与HER2表达水平、淋巴结转移和TNM分期显著相关(P_(均)<0.05)。生存分析表明,血清外泌体HOTTIP高表达组BC患者的5年生存率显著低于低表达组(χ^(2)=5.548,P=0.019);多因素分析显示,血清外泌体HOTTIP高表达是导致BC患者预后不佳的独立危险因素(HR=2.454,95%CI:1.142~7.005,P=0.031)。结论血清外泌体lncRNA HOTTIP在BC中表达上调,其高表达提示肿瘤的恶性进展和患者的不良预后,有望成为BC患者预后评估的非侵入性生物标志物。

Objective To explore the clinical and prognostic value of serum exosomal LncRNA HOTTIP in patients with breast cancer(BC).Methods Exosomes were extracted from serum samples of 98 BC patients,50 benign breast disease(BBD)patients and 50 healthy subjects by kit,and the expression level of HOTTIP in the serum exosomes was detected by RT-qPCR.Furthermore,the relationship among the expression level of HOTTIP,the clinicopathological features and the overall survival was analyzed.Results The expression level of HOTTIP in serum exosomes of the BC patients was significantly higher than that of the BBD patients(t=8.790,P<0.001)and that of the normal healthy people(t=11.540,P<0.001),and the level of HOTTIP in serum exosomes of the BC patients significantly decreased after surgery(t=14.570,P<0.001).Clinicopathological analysis showed that high serum exosomal HOTTIP level was significantly correlated with HER2 expression level,lymph node metastasis and TNM stage(all P<0.05).Further survival analysis showed that the 5-year survival rate of BC patients in the high serum exosomal HOTTIP expression group was significantly lower than that in the low HOTTIP expression group(χ^(2)=5.548,P=0.019).Moreover,multivariate analysis demonstrated that high expression level of serum exosomal HOTTIP was an independent risk factor for the poor prognosis of BC(HR=2.454,95%CI:1.142-7.005,P=0.031).Conclusion The expression of serum exosomal lncRNA HOTTIP is up-regulated in BC,and its high expression indicates the malignant progression of cancer and poor prognosis of BC patients,which implies that serum exosomal lncRNA HOTTIP could be a non-invasive biomarker for the the assessment of prognosis in BC patients.