摘要
目的:分析人类表皮生长因子受体2(HER2)阳性乳腺癌患者中二氢硫酰胺-S-琥珀酰转移酶(DLST)的表达水平,评估其对患者生存预后的影响,同时探讨DLST在HER2阳性乳腺癌发生发展中的潜在机制。方法:(1)使用CancerSEA数据库进行筛选,分析乳腺癌中DLST表达的特异性,再通过Kaplan-Meier Plotter数据库研究DLST对不同分型乳腺癌患者预后的影响。(2)采用CancerSEA数据库探索和验证DLST相关的信号通路。通过免疫沉淀、GST-pull down实验确定在HER2阳性乳腺癌中与DLST相互作用的蛋白。(3)利用TIMER 2.0数据库对DLST与免疫细胞浸润的相关性进行分析。结果:DLST在乳腺癌患者中表达升高,DLST表达越高,HER2阳性乳腺癌患者的预后就会越差并且其生存期也会越短;DLST抑制HER2阳性乳腺癌细胞的凋亡;DLST在HER2阳性乳腺癌的M2巨噬细胞中升高。Neddylation修饰后的PTEN蛋白与DLST存在相互作用。结论:DLST在HER2阳性乳腺癌患者中高表达,与其恶性进程呈正相关,且不利于HER2阳性乳腺癌患者的总体生存预后,初步的机制研究认为DLST与Neddylation修饰后的PTEN蛋白具有相互作用。除此之外,DLST会抑制肿瘤细胞凋亡,并且促进M2型巨噬细胞的浸润。因此,DLST可能成为HER2阳性乳腺癌患者的一种潜在治疗靶标和预后指标。
Objective To study the expression of dihydrolipoamide-S-succinyltransferase(DLST)in human epidermal growth factor receptor 2(HER2)-positive breast cancer patients and its impact on survival prognosis,as well as to clarify its possible involvement in the occurrence and development of HER2-positive breast cancer.Methods(1)Firstly,the CancerSEA database was used to screen for abnormal expression of DLST in various types of cancer,and then the Kaplan-Meier Plotter database was used to analyze the impact of DLST on the prognosis of various types breast cancer patients.(2)The CancerSEA database was used to explore and verify DLST-related signaling pathways.The interaction between DLST and proteins in breast cancer was studied through immunoprecipitation and GST-pull-down experiments.(3)The association between DLST and immune cell infiltration was analyzed using the TIMER 2.0 database.Results DLST was expressed at higher levels in HER2-positive subtype breast cancer patients,and the higher the expression level,the poorer the prognosis and the shorter the survival period of HER2-positive breast cancer patients.In invasive breast cancer,DLST was significantly negatively correlated with the apoptosis pathway.DLST was elevated in M2 macrophages in HER2-positive breast cancer.Neddylation-modified PTEN protein interacted with DLST.Conclusion DLST is highly expressed in breast cancer patient samples,and is positively correlated with the malignant progression of HER2-positive breast cancer,and is not conducive to the overall survival of HER2-positive breast cancer patients.Preliminary mechanism research suggests that DLST interacts with neddylation-modified PTEN protein,and inhibits tumor cell apoptosis and promotes M2 macrophage infiltration.Therefore,this study believes that DLST can be a potential therapeutic target and prognostic marker for clinical HER2-positive breast cancer patients.
作者
凌思惠
彭志强
佟建蒙
谭雅文
谢萍
LING Sihui;PENG Zhiqiang;TONG Jianmeng;TAN Yawen;XIE Ping(Capital Medical University,Beijing 100069;National Center for Protein Sciences,Beijing 102206;Shenzhen Second People's Hospital,Guangdong Shenzhen 518035)
出处
《深圳中西医结合杂志》
2023年第17期6-10,138-139,共7页
Shenzhen Journal of Integrated Traditional Chinese and Western Medicine
基金
国家自然科学基金优秀青年科学基金项目(82122052)
作者简介
凌思惠,女,医学硕士,主要研究方向是蛋白质翻译后修饰;通信作者:谢萍,E-mail:xiep@ccmu.edu.cn,Tel:010-83950275
