南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (04): 488-.

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血浆长链非编码RNA HOTAIR是乳腺癌诊断的潜在生物标志物

张开炯，张毅，罗正莲，刘恋，杨洁，吴立春，张莉，余思思，刘靳波   

  • 出版日期:2016-04-20 发布日期:2016-04-20

Long non-coding RNA HOTAIR in plasma as a potential biomarker for breast cancer diagnosis   

  • Online:2016-04-20 Published:2016-04-20

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摘要： 目的探讨长链非编码RNA HOTAIR在乳腺癌血浆中的表达情况及其对乳腺癌的潜在诊断价值。方法首先采用实时定 量PCR（RT-PCR）的方法检测HOTAIR在24例乳腺癌组织和70例乳腺癌血浆中的表达情况，分析血浆HOTAIR与临床病理特 征相关性；其次采用电化学发光免疫测定法检测血浆中CEA、CA153水平，并建立多元逻辑回归模型分析血浆中HOTAIR相对 于传统标记物CEA和CA153对乳腺癌诊断价值及3项指标联合后诊断价值；最后采用定量PCR的方法检测24位乳腺癌患者术 前和术后血浆中HOTAIR表达水平，并分析24位乳腺癌患者血浆中HOTAIR与组织表达相关性，以评价血浆中的HOTAIR对 患者体内肿瘤动态监测情况。结果与对照组相比，HOTAIR在乳腺癌组织和血浆中表达增高，且血浆中HOTAIR的表达水平 与雌激素受体（ER）（P=0.004）和淋巴结转移明显相关（P=0.010）。通过对血浆中高表达的HOTAIR、CEA及CA153绘制ROC 曲线并建立多元逻辑回归模型，发现HOTAIR曲线下面积（AUC）为0.82（P<0.001），灵敏度和特异性分别为73.3%和93.3%，其 诊断价值高于传统标记物CA153（AUC=0.66，P=0.030）和CEA（AUC=0.52，P=0.001），且3项指标联合后诊断效能（AUC=0.84） 和特异度（96.7%）高于HOTAIR 单独检测。此外，术后血浆中HOTAIR 表达水平较术前明显降低（P<0.0001），且血浆中 HOTAIR表达水平与体内肿瘤表达中度相关（r=0.62，P<0.0001）。结论血浆中高表达的HOTAIR可作为乳腺癌诊断的一个潜 在的新型生物标志物。

Abstract: Objective To investigate the expression of long non-coding RNA HOTAIR in the plasma of breast cancer patients and its value in the diagnosis of breast cancer. Methods HOTAIR levels were measured in 24 tumor tissues and 70 plasma samples from breast cancer patients using quantitative real-time PCR. The correlations of plasma HOTAIR level with the clinicopathological features of the patients were analyzed. A multivariate logistic regression model was established to analyze the value of plasma HOTAIR in comparison with plasma CA153 and CEA levels for breast cancer diagnosis. We further detected HOTAIR levels in the plasma and breast cancer tissues of 24 patients before and after operation and investigated their correlation. Results Breast cancer patients had increased expressions of HOTAIR in the tumor tissues and plasma, and plasma HOTAIR level was significantly correlated with estrogen receptor (ER) level (P=0.004) and lymph node metastasis (P=0.010). Receiver operating characteristic (ROC) curve and the multivariable logistic regression model showed that the area under ROC curve (AUC) of plasma HOTAIR was 0.82 (P<0.001) for breast cancer diagnosis with a diagnostic sensitivity and a specificity of 73.3% and 93.3%, respectively. The diagnostic power and specificity of plasma HOTAIR was much higher than those of CA153 (AUC=0.66, P=0.030) and CEA (AUC=0.52, P=0.001), and the combination of the 3 markers further enhanced the diagnostic power (AUC=0.84) and specificity (96.7%). Plasma HOTAIR level was significantly reduced in the patients after the operation (P<0.0001) and showed a moderate correlation with its expression in tumor tissues (r=0.62, P<0.0001). Conclusion Plasma HOTAIR may serve as a potential biomarker for breast cancer diagnosis.