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巢蛋白和分化簇146在乳腺癌中的表达:通过靶向转移预测早期复发?

Nestin and cluster of differentiation 146 expression in breast cancer: Predicting early recurrence by targeting metastasis?

作者信息

Tampaki Ekaterini Christina, Tampakis Athanasios, Nonni Afroditi, Kontzoglou Konstantinos, Patsouris Efstratios, Kouraklis Gregory

机构信息

1 2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, Athens, Greece.

2 Department of Surgery, University Hospital of Basel, Basel, Switzerland.

出版信息

Tumour Biol. 2017 Mar;39(3):1010428317691181. doi: 10.1177/1010428317691181.

Abstract

The purpose of this study was to investigate the relationship between the expression of stem-cell markers nestin and cluster of differentiation 146 with clinicopathological characteristics in breast cancer and to determine whether a prognostic impact of nestin and CD146 expression exists regarding occurrence of disease relapse in breast cancer. A total of 141 patients who were histologically diagnosed with breast cancer and underwent radical operations from November 2006 to October 2013 in Laiko General Hospital, National and Kapodistrian University of Athens, were enrolled in the study. CD146 and nestin protein expression were evaluated using immunohistochemistry. Nestin expression was observed in 18.4% (26/141) of the cases, while CD146 expression was observed in 35.5% (50/141) of the cases. Nestin expression is significantly higher in younger patients with breast cancer. Nestin and CD146 expression were not correlated with the tumor size and the presence of lymph node metastasis. On the contrary, a significantly higher expression of nestin and CD146 was observed with triple-negative cancers (p < 0.0001 for both markers), low differentiated tumors (p = 0.021 for nestin and p = 0.008 for CD146), and increased Ki-67 expression (p = 0.007 for nestin and p < 0.0001 for CD146). The nestin-positive group of patients and the CD146-positive group of patients presented significantly higher rates of disease recurrence (log-rank test, p = 0.022 for nestin and p = 0.003 for CD146) with a distant metastasis, 30 months after the primary treatment. CD146 but not nestin, however, predicted independently (p = 0.047) disease recurrence. Nestin and CD146 are expressed in breast cancer cells with highly aggressive potency. They might contribute to disease relapse in breast cancer by activating the epithelial-mesenchymal transition pathway and assist tumor neovascularization.

摘要

本研究旨在探讨干细胞标志物巢蛋白(nestin)和分化簇146(CD146)的表达与乳腺癌临床病理特征之间的关系,并确定巢蛋白和CD146表达对乳腺癌疾病复发的预后影响。共有141例于2006年11月至2013年10月在雅典国立与卡波迪斯特里亚大学拉伊科综合医院经组织学诊断为乳腺癌并接受根治性手术的患者纳入本研究。采用免疫组织化学法评估CD146和巢蛋白的蛋白表达。18.4%(26/141)的病例中观察到巢蛋白表达,35.5%(50/141)的病例中观察到CD146表达。巢蛋白在年轻乳腺癌患者中的表达显著更高。巢蛋白和CD146表达与肿瘤大小及淋巴结转移情况无关。相反,在三阴性癌(两种标志物p均<0.0001)、低分化肿瘤(巢蛋白p = 0.021,CD146 p = 0.008)及Ki-67表达增加(巢蛋白p = 0.007,CD146 p<0.0001)的病例中观察到巢蛋白和CD146表达显著更高。巢蛋白阳性患者组和CD146阳性患者组在初次治疗30个月后出现远处转移的疾病复发率显著更高(对数秩检验,巢蛋白p = 0.022,CD146 p = 0.003)。然而,CD146而非巢蛋白可独立预测(p = 0.047)疾病复发。巢蛋白和CD在具有高侵袭潜能的乳腺癌细胞中表达。它们可能通过激活上皮-间质转化途径促进乳腺癌疾病复发并协助肿瘤新生血管形成。

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