Cancer stem cell-related gene periostin: a novel prognostic marker for breast cancer.

Cancer stem cell-related gene periostin: a novel prognostic marker for breast cancer.
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DOI:
10.1371/journal.pone.0046670
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Lu P
Lu P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu D;Xu H;Ren Y;Liu C;Wang X;Zhang H;Lu P

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本研究旨在探讨骨膜蛋白在乳腺癌干细胞中的表达及其临床意义,为乳腺癌的治疗奠定基础。使用流式细胞术分选来自临床标本的CD 44 +/CD 24 −/系肿瘤细胞(CSC)。采用Western blot和免疫组化方法检测CSC细胞和1,086例乳腺癌标本中Periostin的表达情况,并采用免疫荧光双染法测定CSC细胞比例。随后确定骨膜蛋白与临床病理参数和预后之间的关系。因此,与对照组相比,CSC细胞更有可能在NOD/SCID缺陷的小鼠和细胞微球中产生新的肿瘤。与对照细胞相比,CSC细胞中的骨膜蛋白表达更高,并且被发现与CSC化疗抗性相关。此外,在1,086例乳腺癌标本中发现骨膜蛋白表达与CSC比率相关(P = 0.001)。  在1,086例乳腺病例中,共有334例(30.76%)表现出骨膜蛋白高表达。经普适回归和斯皮尔曼回归相关分析,骨膜蛋白与组织学分级、CSC比例、淋巴结转移、肿瘤大小和三阴性乳腺癌相关(均P<0.05)。此外,骨膜蛋白被证明获得一个显着更远的骨转移和更差的疾病特异性生存比那些没有或低表达骨膜蛋白(P = 0.001)。  在考克斯回归检验中,骨膜蛋白被检测为独立的预后因素(P = 0.001)。  总之,发现骨膜蛋白与CSC相关,并且是乳腺癌的独立预后因素。它也可能是乳腺癌的潜在靶点。
We investigated the expression status of periostin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer. CD44+/CD24−/line- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. Periostin expression status was detected in CSC cells and 1,086 breast cancer specimens by Western blot and immunohistochemistry staining, with the CSC ratio determined by immunofluorescence double staining. The relationship between the periostin protein and clinico-pathological parameters and prognosis was subsequently determined. As a result, CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. Periostin protein was expressed higher in CSC cells compared to the control cells and was found to be related to CSC chemotherapy resistance. Moreover, periostin expression was found to be related to the CSC ratio in 1,086 breast cancer specimens (P = 0.001). In total, 334 (30.76%) of the 1,086 breast cases showed high periostin expression. After universal and Spearman regression correlation analysis, periostin was observed to be related to histological grade, CSC ratio, lymph node metastasis, tumor size, and triple-negative breast cancer (all P<0.05). Furthermore, periostin was shown to attain a significantly more distant bone metastasis and worse disease-specific survival than those with none or low-expressed periostin protein (P = 0.001). In the Cox regression test, periostin protein was detected as an independent prognostic factor (P = 0.001). In conclusion, periostin was found to be related to the CSC and an independent prognostic factor for breast cancer. It is also perhaps a potential target to breast cancer.
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