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

作　　者：张婧越 吴开良 吕鉴可 付丽 Jingyue Zhang;Kailiang Wu;Jianke Lv;Li Fu(Department of Breast Cancer Pathology and Research Laboratory,Tianjin Medical University Cancer Institute&Hospital,National Clin�ical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Can�cer,Key Laboratory of Breast Cancer Prevention and Therapy(Ministry of Education),Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院乳腺病理科,国家恶性肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,乳腺癌防治教育部重点实验室,天津市300060

出　　处：《中国肿瘤临床》2022年第18期919-925,共7页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:82173344)资助

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)。IM-PC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。Objective:To investigate the correlation of fatty acid synthase(FASN)expression with the clinicopathological features and pro-gnosis 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 us-ing 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 throm-bus,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 prolifera-tion 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 signal-ing 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.

关 键 词：脂肪酸合成酶 浸润性微乳头状癌 乳腺癌 预后分析 上皮间质转化 

分 类 号：R737.9[医药卫生—肿瘤]