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- 2016
双特异性磷酸酶1在乳腺癌及他莫昔芬耐药病例中的表达变化
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Abstract:
摘要：目的 初步探讨双特异性磷酸酶1(DUSP1)在乳腺癌患者以及乳腺癌他莫昔芬(TAM)耐药患者中的表达变化及其与临床预后的关系。方法 使用TCGA数据库分析DUSP1在1215名不同临床病理特点的乳腺癌患者中的分布和表达情况，使用生存分析数据库分析DUSP1表达水平与乳腺癌患者生存情况的关系；收集8例乳腺癌TAM耐药前后的配对标本进行免疫组化染色，分析DUSP1在耐药前后肿瘤标本中蛋白表达的变化情况。结果 DUSP1在乳腺癌组织中的表达水平显著低于正常乳腺组织(P<0.001)，且在Luminal A亚型中的表达高于其他亚型(P<0.001)；DUSP1的表达水平与乳腺癌患者的总生存(P<0.05)和无复发生存(P<0.001)呈正相关，与接受内分泌治疗的乳腺癌患者的无复发生存呈正相关(P<0.001)；DUSP1在8例TAM耐药患者的配对标本中表达变化未见统计学差异(P>0.05)。结论 在接受内分泌治疗的患者中DUSP1高表达的患者有更好的无复发生存，但是在8例配对标本的检测中未发现DUSP1的表达差异有统计学意义。提示DUSP1与TAM耐药之间关系的探索有待更大样本的临床研究和更深入的细胞和分子生物学实验。
ABSTRACT: Objective To investigate whether dual-specificity phosphatase 1 (DUSP1) plays a role in tamoxifen (TAM) resistance and survival of breast cancer patients. Methods We analyzed DUSP1 mRNA expression in 1215 patient samples in TCGA database and the correlation between DUSP1 mRNA and patient survival using online database. We also investigated the DUSP1 protein level in paired samples from TAM-resistant patients by IHC staining. Results DUSP1 mRNA was significantly decreased in breast cancer tissue compared with normal breast tissue (P<0.001); DUSP1 showed the highest expression in luminal A subtype in all five breast cancer subtypes (P<0.001). Increased DUSP1 mRNA was associated with better overall survival (P<0.05) and relapse-free survival (P<0.001) in breast cancer patients, and was correlated with better relapse-free survival in breast cancer patients receiving endocrine therapy (P<0.001). There was no significant difference in DUSP1 protein level between primary tumor tissue and TAM-resistant tumor tissue from 8 paired TAM resistant patients (P>0.05). Conclusion Increased level of DUSP1 mRNA expression was associated with significantly increased probability of relapse-free survival in patients who received endocrine therapy. The expression of DUSP1 protein in primary tumor tissue and TAM-resistant tumor tissue from the 8 paired samples did not significantly differ, which indicates the role that DUSP1 plays in TAM resistance requires larger sample scale and further investigation in cellular and molecular biology
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