首页|Twist2表达与卵巢癌脉管浸润及预后的相关研究

Twist2表达与卵巢癌脉管浸润及预后的相关研究

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目的:分析Twist2与卵巢癌患者的预后及脉管浸润之间的关系,探索Twist2在卵巢癌脉管浸润中的作用及机制.方法:利用KM plotter分析卵巢癌患者中Twist2 mRNA的表达与卵巢癌总生存率(OS)、无进展生存率(PFS)、肿瘤进展后生存率(PPS)的相关性.利用癌症基因组学数据库cBioportal分析卵巢癌患者中Twist2与脉管浸润的相关性.体外实验:采用Transwell检测Twist2对卵巢癌CAOV3细胞[空白组、阴性对照组(siNC组)、siTwist2组]侵袭、迁移能力的影响,并利用实时荧光定量多聚核苷酸链式反应(realtime-PCR)及蛋白免疫印迹(Western blot)检测分别从RNA水平及蛋白水平检测下调Twist2表达后CAOV3细胞中Twist2、血管内皮生长因子C(VEGFC)表达的变化.结果:①KM plotter在线数据分析结果示,Twist2高表达的卵巢癌患者与不良预后有关,OS(HR 1.24,95%CI 1.01~1.52)、PFS(HR 1.39,95%CI 1.14~1.70)及 PPS(HR 1.37,95%CI 1.08~1.74)差异均有统计学意义(P<0.05);cBioportal分析示,Twist2 mRNA表达与卵巢癌血管浸润(r=0.93,P=0.001)及淋巴管浸润(r=0.89,P=0.009)均呈正相关.②体外实验Transwell检测示,与空白组和siNC组比较,siTwist2组卵巢癌细胞的侵袭及迁移能力显著下降(P<0.05).Realtime-PCR 及 Western blot检测示,与空白组和siNC组比较,siTwist2组中Twist2 mRNA及蛋白、VEGFC mRNA及蛋白的表达均明显下降(P<0.05).结论:卵巢癌中Twist2的表达与肿瘤预后及脉管浸润密切相关,下调Twist2后,细胞迁移及侵袭穿透的细胞数明显减少、VEGFC表达降低,Twist2可能通过VEGFC来诱导肿瘤细胞侵袭转移参与肿瘤脉管浸润,Twist2可能是未来卵巢癌评估预后及靶向治疗的指标之一.
The Correlation between Twist2 Expression and Vascular Infiltration and Prog-nosis in Ovarian Cancer
Objective:To analyze the relationship between Twist2 and the prognosis and vascular infiltration of ovarian cancer patients,and to explore the role and mechanism of Twist2 in vascular infiltration of ovarian cancer.Methods:KM plotter was used to explore the correaltion between Twist2 mRNA expression and overall survival(OS),progression free survival(PFS)and post progression survival(PPS)in ovarian cancer.To analyze the cor-relation between Twist2 and vascular infiltration in ovarian cancer using the cancer genomics database cBioPor-tal.In vitro experiment:Transwell method was employed to determine the role of Twist2 in the invasion and migra-tion abilities of ovarian cancer cell CAOV3[blank group,negative control group(siNC group),siTwist2 group].Uti-lizing Realtime-PCR and Western blot to clarify the changes in Twist2 and VEGFC expression in CAOV3 cells af-ter downregulating Twist2 expression at the RNA and protein levels,respectively.Results:①Online data analysis of KM plotter showed that the ovarian cancer patients with high expression of Twist2 were associated with poor prognosis,with OS(HR 1.24,95%Cl 1.01-1.52),PFS(HR 1.39,95%CI 1.14-1.70)and PPS(HR 1.37,95%CI 1.08-1.74)all showing statistical significance(P<0.05).CBioportal analysis showed that Twist2 mRNA expression was positively correlated with vascular infiltration(r=0.93,P=0.001)and lymphatic infiltration(r=0.89,P=0.009)in ovarian cancer.②Compared with the blank group and siNC group,in vitro experiment Tran-swell assay showed that the invasion and migration ability of ovarian cancer cells in siTwist2 group was significant-ly reduced(P<0.05).In mRNA and protein level,Realtime-PCR and Western blot showed that compared with the blank group and siNC group,the expression of Twist2,as well as VEGFC,were significantly reduced in the siTwist2 group(P<0.05).Conclusions:The expression of Twist2 in ovarian cancer is closely related to tumor prognosis and vascular infiltration.After downregulating Twist2,the number of cells that migrate and invade is sig-nificantly reduced,and the expression of VEGFC is reduced.Twist2 can induce migration and invasion of ovarian cancer cells through VEGFC,which may be one of the indicators for prognosis evaluate and targeted therapy of ovarian cancer in future.

Ovarian cancerTwist2Vascular endothelial growth factor-CPrognosisVascular invasion

蒋婧婧、张红玲、付方方、王恬

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华中科技大学同济医学院附属同济医院妇产科,湖北武汉 430030

卵巢癌 Twist2 血管内皮生长因子C 预后 脉管浸润

2024

实用妇产科杂志
四川省医学会

实用妇产科杂志

CSTPCD北大核心
影响因子:2.564
ISSN:1003-6946
年,卷(期):2024.40(5)