CD44和EPCR mRNA在乳腺癌组织中的表达及其临床意义

目的探讨肿瘤干细胞标记物CD44和EPCR在乳腺癌组织中的相关性及其与乳腺癌临床病理特征的关系。 方法选取2015年1月至4月在北京大学深圳医院行乳腺癌切除术的46例女性患者，用实时荧光定量RT-PCR（qRT-PCR）检测非特殊型浸润性乳腺癌及其配对癌旁正常乳腺组织中CD44及EPCR的mRNA表达水平，分析其与临床病理特征的关系，并探讨两者的相关性。 结果（1）荧光定量RT-PCR结果显示CD44 mRNA在乳腺癌组织中的表达明显高于癌旁正常乳腺组织，差异具有统计学意义（t=2.486，P=0.017），在ER阳性乳腺癌明显低于ER阴性组、在正常乳腺样型的三阴型乳腺癌明显高于非正常乳腺样型的三阴型组，差异具有统计学意义（t=-2.332，P=0.024；t=-4.209，P<0.01），但与患者年龄、肿瘤大小、组织学分级、淋巴结转移及临床分期无关（P>0.05）；（2）EPCR mRNA在乳腺癌组织中的表达明显高于癌旁正常乳腺组织，差异具有统计学意义（t=4.028，P<0.01），与乳腺癌的肿瘤大小（t=2.998，P<0.01）、组织学分级（t=4.082，P<0.01）、淋巴结转移（t=2.152，P=0.037）、临床分期（t=-2.378，P=0.022）、ER（t=-5.585，P<0.01），PR（t=-3.896，P<0.01）及增殖指数Ki67（t=2.197，P=0.033）相关，差异具有统计学意义。但与患者的年龄及HER2无关（P>0.05），在三阴型（尤其是基底样型）乳腺癌及Luminal B型乳腺癌中的相对表达水平也明显高于非三阴型组及非Luminal B型组，差异具有统计学意义（t=9.163，P<0.01；t=3.653，P=0.003）；（3）在乳腺癌中，CD44及EPCR mRNA的表达呈显著正相关（r_s=0.540，P<0.01）。 结论乳腺癌干细胞标志物CD44及EPCR在乳腺癌组织中均明显表达上调，2者具有正相关，但EPCR与更多的临床病理特征相关，提示EPCR可更好地预测乳腺癌的淋巴结转移及较高临床分期等不良预后，并推测CD44及EPCR可能所标记为2种不同表型的乳腺癌干细胞。

Clinical significance of CD44 and EPCR mRNA expression in breast cancer

ObjectiveTo detect the expression of the stem cell markers CD44 and EPCR in breast cancer and analyze their correlation with clinicopathological parameters. MethodsQuantitative real-time PCR (qRT-PCR) was performed to measure the expression of CD44 and EPCR mRNAs in invasive breast carcinoma of no special type (IBC-NST) tissues and matched normal breast tissues from 46 women. ResultsThe expression level of CD44 mRNA was significantly higher in IBC-NST than in adjacent normal tissues (t=2.486, P=0.017), in ER- IBC-NST than in ER+ IBC-NST tissues (t=-2.332, P=0.024), and in normal breast-like triple negative IBC-NST than in non-normal breast-like triple negative IBC-NST tissues(t=-4.209, P<0.01). However, there was no significant correlation between CD44 expression and patient age, tumor size, histological grade, clinical stage, or lymph node metastasis (P>0.05). The expression level of EPCR mRNA in IBC-NST tissues was significantly higher than that in adjacent normal tissues (t=4.028, P<0.01). The expression of EPCR mRNA was significantly related to tumor size (t=2.998, P<0.01), histological grade (t=4.082, P<0.01), lymph node metastasis (t=2.152, P=0.037), clinical stage (t=-2.378, P=0.022), ER status (t=-5.585, P<0.01), PR status (t=-3.896, P<0.01), and Ki-67 index (t=2.197, P=0.033), but not to patient age and HER-2 status (P>0.05). In addition, the expression level of EPCR mRNA was significantly higher in triple negative (especially basal-like subtype) than in non-triple negative tissues (t=9.163, P<0.01), and in luminal B IBC-NST than in non-luminal B IBC-NST tissues (t=9.163, P<0.01; t=3.653, P=0.003). There was a positive correlation between CD44 and EPCR mRNA expression (r_s=0.540, P<0.01). ConclusionThe expression of the stem cell markers CD44 and EPCR in breast cancer is significantly higher and positively correlated in IBC-NST, but the expression of EPCR is associated with more clinicopathological features, suggesting that EPCR can better predict lymph node metastasis and a poor prognosis in breast cancer. It is speculated that CD44 and EPCR may represent respective markers of two different types of breast cancer stem cells.