HMGCS1表达对食管鳞癌细胞转移能力及食管鳞癌患者预后的影响  

Effect of HMGCS1 expression on metastatic ability of ESCC cells and prognosis of ESCC patients

作　　者：马天云 罗超 刘龙飞 张莉[1] 刘当云 王其龙[1] MA Tianyun;LUO Chao;LIU Longfei;ZHANG Li;LIU Dangyun;WANG Qilong(Department of Central Laboratory,the Affiliated Huai’an No.1 People’s Hospital,Nanjing Medical University,Huai’an 223300,China)

机构地区：[1]南京医科大学附属淮安第一医院中心实验室,江苏淮安223300

出　　处：《南京医科大学学报（自然科学版）》2022年第10期1357-1363,1458,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省自然科学基金(BK20211111);南京医科大学科技发展基金(NMUB20210141)。

摘　　要：目的:探讨3-羟基-3-甲基戊二酰辅酶A合酶1(3-hydroxy-3-methylglutaryl-CoA synthase 1,HMGCS1)在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)及食管鳞癌肺转移患者中表达的临床意义及其对食管鳞癌细胞转移能力的影响。方法:通过收集南京医科大学附属淮安第一医院6例食管鳞癌手术患者组织样本,根据其随访最终信息分为未转移组和肺转移组,对两组样本进行蛋白质谱测序分析,筛选差异表达的蛋白质HMGCS1,通过GEPIA数据库进行验证。Western blot及qPCR检测食管上皮细胞及ESCC癌细胞中HMGCS1表达水平。免疫组织化学方法对121例随访信息完善的食管鳞癌患者组织芯片进行染色,检测HMGCS1表达。采用Cox生存风险比例模型分析ESCC患者生存的风险因素,同时采用多变量相关性分析HMGCS1与ESCC患者临床病理之间的关系,采用Kaplan-Meier法分析HMGCS1对ESCC患者预后的影响。构建HMGCS1过表达质粒转染食管鳞癌细胞,利用划痕及Transwell检测细胞的迁移及侵袭能力。结果:与未发生转移的食管鳞癌患者癌组织相比,肺转移患者肿瘤组织中有51种蛋白下调,45种蛋白上调,其中HMGCS1在肺转移患者食管鳞癌组织中的表达显著低于未转移患者。GEPIA数据显示HMGCS1在食管鳞癌中表达也是下调的。Western blot及qPCR结果表明食管鳞癌细胞中HMGCS1表达显著低于正常食管上皮细胞。121例食管鳞癌患者组织芯片免疫组织化学染色结果证实,HMGCS1在食管鳞癌中的表达显著低于正常食管组织,且有淋巴结转移的患者其表达显著低于无淋巴结转移患者(P <0.05)。Cox生存风险分析显示,T分期[HR:2.118(1.020~4.399)]、淋巴结转移[HR:2.127(1.466~5.584)]、HMGCS1低表达[HR:0.413(0.211~0.807)]是食管鳞癌患者的生存风险因素。多变量相关性分析则显示,HMGCS1表达与淋巴结转移显著相关。Kaplan-Meier生存分析显示,HMGCS1低表达患者预后较差。食管鳞癌细�Objective:To investigate the potential association of 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1)expression with the prognosis of patients with esophageal squamous cell carcinoma(ESCC)and to explore the biological effects of HMGCS1 on the metastatic ability of ESCL cells. Methods:Tissue samples from 6 patients who underwent ESCC surgeries in our hospital were collected and divided into non-metastatic and lung metastatic groups. Protein spectrum sequencing analysis together with GEPIA database was performed to screen differentially expressed proteins. Western blot and qPCR were used to determine HMGCS1expression in esophageal epithelial cells and ESCC cells. Immunohistochemical staining was performed to determine HMGCS1expression in tissue sections from 121 patients with ESCC. Cox proportional survival risk model was enrolled to analyze the survival risk factors of ESCC patients,and multivariate correlation analysis was used for the analysis of the association of HMGCS1 with the clinicopathology of ESCC patients. Furthermore,Kaplan-Meier analysis was employed to analyze the effect of HMGCS1 on the prognosis of ESCC patients. The migration and invasion ability of ESCC cells were detected by scratch and Transwell. Results:We identified 45 significantly up-regulated and 51 down-regulated(including HMGCS1)proteins in the tumor tissues of patients with lung metastasis,compared with those without metastasis. GEPIA verified that HMGCS1 was down-regulated in esophageal cancer. Western blot and qPCR results further validated that HMGCS1 expression in ESCC cells was significantly lower than that in normal esophageal epithelium. Immunohistochemical staining of 121 patients with ESCC confirmed that the expression of HMGCS1 in ESCC was significantly lower than that in normal esophageal tissues. Additionally,the expression of HMGCS1 in patients with lymph node metastasis was significantly lower than that in patients without lymph node metastasis(P < 0.05). Cox survival risk analysis showed that T stage[HR:2.118(1.020~4.39

关 键 词：食管鳞癌 3-羟基-3-甲基戊二酰辅酶A合酶1 预后 转移 

分 类 号：R735.1[医药卫生—肿瘤]