FAT4在三阴性乳腺癌组织中的表达及其临床意义

背景与目的:三阴性乳腺癌(TNBC)因为缺乏有效的治疗靶点,临床治疗措施有限,预后极差。本研究旨在探讨脂肪非典型钙黏蛋白4(FAT4)在TNBC组织中的表达及其临床意义,以期为该病的治疗提供新的策略。方法:采用qRT-PCR和Western blot法检测10例TNBC患者新鲜癌组织及对应癌旁组织标本中FAT4 mRNA及蛋白质的表达;免疫组化法检测60例TNBC患者癌组织与癌旁组织石蜡标本中FAT4的表达,分析FAT4的表达水平与TNBC患者临床病理特征及预后的关系。结果:10例新鲜标本中,TNBC组织中FAT4 mRNA及蛋白的相对表达量均较癌旁组织明显降低(均P<0.05),以癌旁组织为参考,TNBC组织中FAT4 mRNA相对表达量为0.482±0.092,蛋白相对表达量为0.437±0.082。60例石蜡标本分中,FAT4在TNBC组织中的阳性率明显低于癌旁组织(23.33%vs.71.67%,χ^2=28.104,P<0.001);FAT4的表达与淋巴结状态(P=0.034)、肿瘤大小(P=0.001)、TNM分期(P=0.028)、组织学分级(P=0.023)和Ki-67指数(P=0.031)明显有关,而与年龄(P=0.744)和月经状态(P=0.933)无关;FAT4阳性表达患者的无病生存期(DFS)明显长于FAT4阴性表达患者(42.0个月vs.34.6个月,P=0.037);多因素Cox风险比例模型分析显示,FAT4高表达是TNBC患者DFS的独立保护因素(HR=0.52,95%CI=0.29~0.98,P=0.041)。结论:FAT4在TNBC组织中呈低表达,FAT4的低表达与TNBC患者的恶性生物学特征及不良预后密切相关。

FAT4 expression in triple negative breast cancer and its clinical significance

Background and Aims:Triple negative breast cancer(TNBC)has an extremely poor prognosis because of the lack of effective therapeutic targets and limited treatment options in clinical practice.This study was designated to investigate the expression of FAT atypical cadherin 4(FAT4)in TNBC tissue and its clinical significance,so as to provide a new treatment strategy for this disease.Methods:The mRNA and protein expressions of FAT4 in fresh paired tumor and adjacent tissue samples from 10 TNBC patients were determined by RT-PCR and Western blot,respectively.Then,FAT4 expressions in the paraffin-embedded specimens of paired tumor and adjacent tissue from 60 TNBC patients were examined by immunohistochemical staining,and the relations of FAT4 expression with the clinicopathologic features and prognosis of the TNBC patients were analyzed.Results:In the 10 paired fresh tissue samples,the relative expression levels of FAT4 mRNA and protein were significantly lower in TNBC tissue than those in adjacent tissue(both P<0.05),using adjacent tissue as a reference,the mRNA expression value was 0.482±0.092 and protein expression value was 0.437±0.082 respectively.In the 60 paraffin-embedded specimens,the positive expression rate of FAT4 protein in TNBC tissue was significantly lower than that in adjacent tissue(23.33%vs.71.67%,χ^2=28.104,P<0.001);the FAT4 protein expression was significantly associated with lymph node status(P=0.034),tumor size(P=0.001),TNM stage(P=0.028),histological grade(P=0.023)and Ki-67 index(P=0.031),but irrelevant to age(P=0.744)and menstrual status(P=0.933);the disease-free survival(DFS)in TNBC patients with positive FAT4 expression was significantly longer than that in those with negative FAT4 expression(42.0 months vs.34.6 months,P=0.037);Cox multivariate proportional hazard model shown that high FAT4 expression of was an independent protective factor for DFS in TNBC patients(HR=0.52,95%CI=0.29–0.98,P=0.041).Conclusion:FAT4 expression is decreased in TNBC tissue,and low FAT4 expression is closely related to the malignant biological characteristics and unfavorable outcomes of TNBC patients.