张婧越, 吴开良, 吕鉴可, 付丽. ­脂肪酸合成酶在乳腺浸润性微乳头状癌中的表达及作用研究[J]. 中国肿瘤临床, 2022, 49(18): 919-925. DOI: 10.12354/j.issn.1000-8179.2022.20220496
引用本文: 张婧越, 吴开良, 吕鉴可, 付丽. ­脂肪酸合成酶在乳腺浸润性微乳头状癌中的表达及作用研究[J]. 中国肿瘤临床, 2022, 49(18): 919-925. DOI: 10.12354/j.issn.1000-8179.2022.20220496
Jingyue Zhang, Kailiang Wu, Jianke Lv, Li Fu. Expression and role of fatty acid synthase in invasive micropapillary carcinoma of breast[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2022, 49(18): 919-925. DOI: 10.12354/j.issn.1000-8179.2022.20220496
Citation: Jingyue Zhang, Kailiang Wu, Jianke Lv, Li Fu. Expression and role of fatty acid synthase in invasive micropapillary carcinoma of breast[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2022, 49(18): 919-925. DOI: 10.12354/j.issn.1000-8179.2022.20220496

­脂肪酸合成酶在乳腺浸润性微乳头状癌中的表达及作用研究

Expression and role of fatty acid synthase in invasive micropapillary carcinoma of breast

  • 摘要:
      目的  探讨脂肪酸合成酶(fatty acid synthase,FASN)表达与乳腺浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)临床病理学特征及预后的相关性。
      方法  选取2010年1月至2015年12月天津医科大学肿瘤医院105例乳腺IMPC组及105例乳腺浸润性导管癌-非特殊类型(invasive ductal carcinoma-no special type, IDC-NOS)组的病例,行FASN免疫组织化学法染色后进行统计学分析。利用CCK8、划痕实验检测FASN对T47D乳腺癌细胞增殖、迁移能力的影响。利用蛋白免疫印迹实验检测FASN对Wnt/β-catenin信号通路及上皮间质转化(epithelial-mesenchymal transition, EMT)的影响。
      结果  FASN在IMPC中的表达为61.0%(64/105),显著高于IDC-NOS的31.4%(33/105),两者比较差异具有统计学意义(P<0.001)。IMPC中的FASN表达与患者脉管癌栓、N分期、Ki-67表达呈正相关(P<0.05),与IMPC患者的无病生存(disease-free survival, DFS)期和总生存(overall survival, OS)期呈负相关(P<0.01)。FASN高表达是IMPC患者DFS和OS降低的独立危险因素(P<0.05)。敲低FASN后T47D细胞的增殖、迁移能力显著下降(P<0.001)。FASN促进T47D细胞中Wnt/β-catenin通路及EMT。
      结论  FASN通过Wnt/β-catenin信号通路促进EMT导致乳腺癌细胞增殖、迁移。FASN高表达与IMPC高侵袭、高转移等临床病理学特征呈正相关,是预测IMPC患者预后的独立危险因素。

     

    Abstract:
      Objective  To investigate the correlation of fatty acid synthase (FASN) expression with the clinicopathological features and prognosis of invasive micropapillary carcinoma (IMPC) of the breast.
      Methods  105 cases of breast IMPC patients and 105 cases of invasive ductal carcinoma-no special type (IDC-NOS) patients that were admitted to Tianjin Medical University Cancer Institute & Hospital between the period of January 2010 to December 2015 were selected, and FASN immunohistochemical staining was performed for statistical analysis. The effects of FASN on the proliferation and migration of T47D breast cancer cells were investigated by CCK8 and scratch experiments. Changes in the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT) key proteins owing to FASN were assessed using Western blot.
      Results  The expression of FASN in IMPC (61.0%, 64/105) was significantly higher than that in IDC-NOS (31.4%, 33/105), and the difference was statistically significant (P<0.001). Its expression in IMPC patients was positively correlated with vascular tumor thrombus, N stage, and Ki-67 expression (P<0.05) and negatively correlated with disease-free survival (DFS) and overall survival (OS) period (P<0.01). The high expression of FASN was an independent risk factor for the decreased DFS and OS in IMPC patients (P<0.05). The proliferation and migration ability of T47D breast cancer cells were significantly decreased after the knockdown of FASN (P<0.001). FASN promoted the Wnt/β-catenin signaling pathway and EMT in T47D breast cancer cells.
      Conclusions  FASN promotes EMT through Wnt/β-catenin signaling pathway, leading to the proliferation and migration of T47D breast cancer cells. The high expression of FASN is positively correlated with clinicopathological factors such as high invasion and metastasis of IMPC, and it is an independent risk factor for predicting the prognosis of IMPC patients.

     

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