Clinical Implications of Stem Cell Gene Oct-4 Expression in Breast Cancer
Clinical Implications of Stem Cell Gene Oct-4 Expression in Breast Cancer
复制标题
干细胞基因 Oct-4 表达在乳腺癌中的临床意义
DOI：
10.1097/sla.0b013e318214c54e
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发表时间：
2011-06-01
影响因子：
9
通讯作者：
Lu, Ping
中科院分区：
文献类型：
--
作者：
Liu, Cai-gang;Lu, Ying;Lu, Ping
目的：探讨干细胞基因在乳腺癌中的表达及其与乳腺癌临床病理特征和预后的关系。背景：目前，干细胞分化相关基因及其与乳腺癌临床病理特征和预后的关系尚不清楚。材料与方法：流式细胞术筛选CD 44 +/CD 24 −肿瘤细胞。RT 2 Profiler™ PCR Array检测CD 44 +/CD 24 −肿瘤细胞和非CD 44 +/CD 24 −肿瘤细胞之间的差异表达基因。采用免疫组化方法检测干细胞基因Octamer-4（Oct-4）的表达，并分析其与乳腺癌临床病理参数的关系。结果：检测到7种不同的基因，包括干细胞分化相关因子（CD 44，Oct-4和巢蛋白），细胞周期调节因子（APC和CDC 2）和生长因子（HGF和TGF），在CD 44 +/CD 24 −肿瘤细胞和非CD 44 +/CD 24 −肿瘤细胞之间表达显著不同。Oct-4蛋白在癌组织中的表达显著高于癌旁组织（P = 0.001）。Oct-4蛋白的表达与乳腺癌的组织学类型、淋巴结转移和分子类型有关（P值分别为0.001、0.006和0.001）。经生存分析后，Oct-4蛋白高表达的病例术后疾病特异性生存率显著低于Oct-4蛋白无表达或低表达的病例（P = 0.001）。考克斯回归分析显示，肿瘤大小、组织学类型、疾病分期、淋巴结转移、Her-2和Oct-4为独立预后因素（P值分别为0.031、0.012、0.001、0.002、0.030和0.003）。结论：Oct-4在CD 44 +/CD 24 −肿瘤细胞中高表达，可能是乳腺癌发生、发展和分化的潜在生物标志物。
Purpose:To explore the expression of stem cell genes in breast cancer and the relationship between stem cell gene expression and clinical and pathological characteristics and prognosis of breast cancer. Background:By now, stem cell differentiation-related genes and the relationship between the genes and clinic-pathological characteristics and prognosis of breast cancer are still unclear. Materials and Methods:CD44+/CD24− tumor cells were selected by Flow cytometry. The differential expression of genes between CD44+/CD24− tumor cells and non-CD44+/CD24− tumor cells were detected by RT2 Profiler™ PCR Array. The expression of stem cell gene Octamer-4 (Oct-4) was analyzed by immunohistochemistry staining and the relationship between Oct-4 and clinicopathological parameters of breast cancer was determined. Results:Seven different genes including stem cell differentiation-related factors (CD44, Oct-4, and nestin), cell cycle regulators (APC and CDC2), and growth factors (HGF and TGF) were detected as significantly differently expressed between CD44+/CD24− tumor cells and non-CD44+/CD24− tumor cells. Oct-4 protein expressed significantly higher in cancerous tissues than adjacent-tumor tissues (P = 0.001). Moreover, we observed that the expression of Oct-4 protein was related to histological type, lymph node status and molecular type of breast cancer (P = 0.001, 0.006, and 0.001, respectively). After survival analysis, the cases with highly expressed Oct-4 protein attained a significantly poorer postoperative disease-specific survival than those with none/low expressed Oct-4 protein (P = 0.001). In the Cox regression test, tumor size, histological type, disease stage, lymph node metastasis, Her-2 and Oct-4 were detected as the independent prognostic factors (P = 0.031, 0.012, 0.001, 0.002, 0.030, and 0.003, respectively). Conclusions:Oct-4 was highly expressed in CD44+/CD24− tumor cells, and may be a potential biomarker for the initiation, progression, and differentiation of breast cancer.