Jin Feng, Liu Caigang, Guo Yang, Chen Hao, Wu Yunfei
Department of Breast Surgery, General Surgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Oncol Lett. 2013 May;5(5):1549-1553. doi: 10.3892/ol.2013.1249. Epub 2013 Mar 12.
The aim of this study was to investigate the correlation between Girdin and PI3K in breast cancer stem cells and the clinical implications of the co-expression of these two proteins in breast cancer patients. CD44/CD24 tumor cells from the MD-231 cell line were sorted by flow cytometry. The expression status of Girdin and PI3K proteins was detected using western blotting and immunohistochemical staining. The relationship between Girdin and PI3K proteins and clinicopathological parameters was analyzed in 820 breast cancer patients. Girdin and PI3K proteins were more highly expressed in CD44/CD24 tumor stem cells compared to the control group and Girdin and PI3K proteins were co-immunoprecipitated in the MD-231 cell line. Of the 820 enrolled breast cancer patients, Girdin and PI3K proteins were expressed in 295 (35.98%) and 492 (60.00%) cases, respectively. There were 162 (19.76%) cases which co-expressed Girdin and PI3K proteins. Univariate and multivariate analyses indicated that the co-expression of Girdin and PI3K proteins correlated with histological type, metastatic nodes and distant metastasis (P=0.01, 0.001 and 0.001, respectively). After analyzing survival rates, cases with Girdin and PI3K co-expression were shown to attain a significantly increased distant metastasis rate and poorer postoperative, disease-specific survival compared to those with Girdin and PI3K co-expression (P=0.001). In the Cox regression test, Girdin and PI3K co-expression was detected as an independent prognostic factor (P=0.001). Girdin may regulate the biological behavior of breast cancer via the PI3K/Akt/mTOR pathway, and thus, serve as a potential new target for breast cancer treatment.
本研究旨在探讨乳腺癌干细胞中Girdin与PI3K之间的相关性，以及这两种蛋白共表达在乳腺癌患者中的临床意义。通过流式细胞术对MD-231细胞系中的CD44/CD24肿瘤细胞进行分选。采用蛋白质免疫印迹法和免疫组织化学染色检测Girdin和PI3K蛋白的表达状态。分析820例乳腺癌患者中Girdin和PI3K蛋白与临床病理参数之间的关系。与对照组相比，Girdin和PI3K蛋白在CD44/CD24肿瘤干细胞中表达更高，且在MD-231细胞系中Girdin和PI3K蛋白可进行共免疫沉淀。在820例纳入研究的乳腺癌患者中，Girdin蛋白和PI3K蛋白分别在295例（35.98%）和492例（60.00%）中表达。有162例（19.76%）同时表达Girdin和PI3K蛋白。单因素和多因素分析表明，Girdin和PI3K蛋白的共表达与组织学类型、转移淋巴结及远处转移相关（P值分别为0.01、0.001和0.001）。分析生存率后发现，与Girdin和PI3K未共表达的患者相比，Girdin和PI3K共表达的患者远处转移率显著增加，术后疾病特异性生存率更差（P=0.001）。在Cox回归检验中，Girdin和PI3K共表达被检测为独立的预后因素（P=0.001）。Girdin可能通过PI3K/Akt/mTOR途径调节乳腺癌的生物学行为，因此可作为乳腺癌治疗的潜在新靶点。
