ETV5 在高级别浆液性卵巢癌中的生物学和预后价值。

Biological and prognostic value of ETV5 in high-grade serous ovarian cancer.

机构信息

Department of Pathology, NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases/The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832003, China.

Department of Pathology, Shenzhen Traditional Chinese Medicine hospital, Shenzhen, 518033, China.

出版信息

J Ovarian Res. 2021 Nov 4;14(1):149. doi: 10.1186/s13048-021-00899-6.

DOI:10.1186/s13048-021-00899-6

PMID:34736492

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8570011/

Abstract

BACKGROUND

ETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates.

RESULTS

Bioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p < 0.05). qRT-PCR showed that ETV5 was significantly overexpressed in HGSOC tissues than in fallopian tube tissues (p < 0.05). qRT-PCR and western blotting assays demonstrated that ETV5 was relatively highly expressed in OC cell lines. ETV5 overexpression was positively associated with poor survival in HGSOC patients, therefore making it a high-risk factor for HGSOC progression. Furthermore, ETV5 promoted the proliferation, migration, and invasion capabilities of HGSOC cells.

CONCLUSION

ETV5 has a carcinogenic effect in HGSOC and can be used as a clinically effective biomarker to determine the prognosis of HGSOC patients.

摘要

背景

ETS 转录因子被认为可以作为参与各种生物过程的基因表达的正调控或负调控因子。据报道，ETS 变体转录因子 5（ETV5）作为 ETS 家族的关键成员，主要在各种恶性肿瘤中作为潜在的癌基因发挥作用。然而，ETV5 在高级别浆液性卵巢癌（HGSOC）中的作用和机制尚未阐明。

方法

采用定量实时聚合酶链反应（qRT-PCR）检测 87 例 HGSOC 组织和 35 例正常输卵管组织中 ETV5 信使核糖核酸（mRNA）的表达。Western blot 和 qRT-PCR 检测 6 种卵巢癌细胞（OC）和人胚胎细胞系中 ETV5 的蛋白和 mRNA 表达。采用 HGSOC 细胞系的 ETV5 敲低或过表达、细胞计数试剂盒-8、集落形成和 Transwell 检测，检测 HGSOC 细胞的增殖、侵袭和迁移能力。采用卡方检验分析 HGSOC 患者的临床病理特征。采用 Kaplan-Meier 法进行生存分析，采用对数秩检验分析 ETV5 表达与 HGSOC 患者预后的相关性。采用 Cox 回归模型进行单因素和多因素分析，确定相关临床协变量的独立意义。

结果

生物信息学分析表明，OC 中 ETV5 表达明显上调（p<0.05）。qRT-PCR 显示，HGSOC 组织中 ETV5 的表达明显高于输卵管组织（p<0.05）。qRT-PCR 和 Western blot 检测表明，ETV5 在 OC 细胞系中相对高表达。ETV5 过表达与 HGSOC 患者的不良生存相关，因此是 HGSOC 进展的高危因素。此外，ETV5 促进了 HGSOC 细胞的增殖、迁移和侵袭能力。