Department of Biochemistry and Molecular Biology, University of Louisville-Health Sciences Center, Louisville, KY 40292, USA.
Horm Cancer. 2013 Aug;4(4):208-21. doi: 10.1007/s12672-013-0141-2. Epub 2013 Apr 9.
Expression of protein tyrosine phosphatase PTP4A2 (also known as PRL2) has been examined in a variety of human carcinomas, although its role in breast cancer remains inconclusive. Since the majority of previous breast cancer studies utilized tissue biopsies composed of heterogeneous cell populations, we hypothesized that an examination of PTP4A2 expression in carcinoma cells isolated by laser capture microdissection (LCM) would provide a more accurate means of assessing its predictive value. From investigations of 247 human breast cancer biopsies collected under standardized, stringent conditions, total RNA was extracted from LCM-procured carcinoma cells to perform microarray analyses to identify gene signatures associated with breast cancer behavior. Expression of PTP4A2 was corroborated by real-time quantitative polymerase chain reaction (qPCR) and referenced to estrogen and progesterone receptor levels. Patient outcomes for overall and disease-free survival were more favorable (p = 0.004 and p = 0.001, respectively) when the expression of PTP4A2 in breast carcinomas was increased compared to patients with biopsies with decreased PTP4A2 levels. PTP4A2 expression determined either by microarray or qPCR was elevated in either estrogen receptor (ER)-positive or progestin receptor (PR)-positive breast cancer biopsies compared to ER-negative or PR-negative biopsies. However, PTP4A2 expression was only correlated with overall survival in PR-positive breast carcinomas. These data suggest that PTP4A2 mRNA expression alone may serve as a biomarker for prediction of a breast cancer patient's risk of recurrence and overall survival.
蛋白酪氨酸磷酸酶 PTP4A2(也称为 PRL2)的表达已在多种人类癌中进行了检查,尽管其在乳腺癌中的作用仍不确定。由于大多数先前的乳腺癌研究都利用了由异质细胞群体组成的组织活检,因此我们假设通过激光捕获显微切割(LCM)分离的癌细胞中 PTP4A2 表达的检查将提供更准确的评估其预测价值的方法。从在标准化、严格条件下收集的 247 个人类乳腺癌活检中进行的研究中,从 LCM 获得的癌细胞中提取总 RNA,以进行微阵列分析以鉴定与乳腺癌行为相关的基因特征。通过实时定量聚合酶链反应(qPCR)证实了 PTP4A2 的表达,并参考了雌激素和孕激素受体水平。与 PTP4A2 水平降低的活检患者相比,当乳腺癌中 PTP4A2 的表达增加时,患者的总体生存率和无病生存率更为有利(p = 0.004 和 p = 0.001)。通过微阵列或 qPCR 确定的 PTP4A2 表达在雌激素受体(ER)阳性或孕激素受体(PR)阳性乳腺癌活检中均高于 ER 阴性或 PR 阴性活检。然而,PTP4A2 表达仅与 PR 阳性乳腺癌的总体生存率相关。这些数据表明,PTP4A2 mRNA 表达本身可能可作为预测乳腺癌患者复发风险和总体生存率的生物标志物。