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BTG1作为子宫内膜癌一种新的预后标志物可抑制恶性肿瘤。

BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma.

作者信息

Li Yibing, Huo Jianing, He Junjian, Zhang Yunzheng, Ma Xiaoxin

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China.

出版信息

Cancer Cell Int. 2020 Oct 7;20:490. doi: 10.1186/s12935-020-01591-3. eCollection 2020.

DOI:10.1186/s12935-020-01591-3
PMID:33041670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7542768/
Abstract

BACKGROUND

Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC.

METHODS

Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot.

RESULTS

We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs.

CONCLUSIONS

BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.

摘要

背景

子宫内膜癌(EC)是女性生殖系统三大主要恶性肿瘤之一。近年来,EC的发病率和死亡率有所上升。B细胞易位基因1(BTG1)是一种抗增殖基因,可调节多种肿瘤的发生发展,但在EC中尚无关于该基因的研究。

方法

基于癌症基因组图谱(TCGA)数据库,我们使用了多种生物信息学工具和数据库来探究BTG1的表达及预后情况。我们通过qRT-PCR验证了BTG1在EC中的表达及预后,并分析了相关临床病理参数。我们通过生物信息学网站对EC患者中的BTG1及相关基因进行功能富集,并分析了BTG1的miRNA靶点及相互作用蛋白网络。采用细胞增殖、伤口愈合、transwell侵袭和细胞凋亡实验来检测BTG1对子宫内膜癌细胞(ECCs)恶性生物学行为的影响。使用蛋白质免疫印迹法检测BTG1对上皮-间质转化(EMT)过程的影响。

结果

我们基于TCGA分析了BTG1的表达及预后,发现BTG1低表达与EC预后不良相关。qRT-PCR提示BTG1在EC中表达较低。BTG1表达与总生存期(OS)缩短显著相关。临床病理分析表明,BTG1的表达与浸润深度和国际妇产科联盟(FIGO)分期有关。EC的病理组织类型、生育史、淋巴转移、绝经、雌激素受体(ER)、孕激素受体(PR)及诊断年龄无关。功能富集分析表明,BTG1在调节胚胎发育、肿瘤发生、凋亡和细胞周期中起重要作用。生物学行为实验表明,BTG1抑制ECCs的增殖、迁移和侵袭,并促进ECCs的凋亡。蛋白质免疫印迹表明,BTG1抑制ECCs的EMT过程。

结论

BTG1作为一种肿瘤抑制基因,在EC的发生发展中起重要作用。我们认为BTG1可作为EC潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/925e4bf5d2d2/12935_2020_1591_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/925e4bf5d2d2/12935_2020_1591_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/c1158a157407/12935_2020_1591_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/098fd912892d/12935_2020_1591_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/20e1a1d74981/12935_2020_1591_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37dd/7542768/925e4bf5d2d2/12935_2020_1591_Fig8_HTML.jpg

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