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一个关键的血管生成相关基因MEOX2可能是乳腺癌一个有前景的生物标志物候选者。

A Crucial Angiogenesis-Associated Gene MEOX2 Could Be a Promising Biomarker Candidate for Breast Cancer.

作者信息

Wang Huxia, Tang Yanan, Yang Xiaomin, Wang Weiyi, Han Pihua, Zhao Jing, He Sai, Liu Peijun

机构信息

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Mammary Department, Shaanxi Provincial Cancer Hospital, Xi'an, China.

出版信息

Front Oncol. 2022 May 9;12:759300. doi: 10.3389/fonc.2022.759300. eCollection 2022.

DOI:10.3389/fonc.2022.759300
PMID:35615155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9124839/
Abstract

BACKGROUND

Angiogenesis plays a critical role in the growth and metastasis of breast cancer and angiogenesis inhibition has become an effective strategy for cancer therapy. Our study aimed to clarify the key candidate genes and pathways related to breast cancer angiogenesis.

METHODS

Differentially expressed genes (DEGs) in the raw breast cancer (BRCA) gene dataset from the Cancer Genome Atlas (TCGA) database were identified and gene ontology analysis of the DEGs was performed. Hub genes were subsequently determined using the Gene Expression Omnibus database. The expression of the mesenchyme homeobox 2 (MEOX2) in breast cancer cells and tissues was assessed by quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. The prognostic value of the MEOX2 gene in breast cancer tissue was evaluated with the Kaplan-Meier plotter.

RESULTS

A total of 61 angiogenesis-related DEGs were identified in the TCGA dataset, among which the gene MEOX2 was significantly down-regulated. GO functional annotation and pathway enrichment analyses showed that MEOX2 was significantly enriched in the regulation of vasculature development. The IHC results confirmed that MEOX2 expression was repressed in breast cancer tissues and the relatively low level indicated the tissue was densely vascularized. Moreover, MEOX2 expression was significantly elevated in breast cancer cells after treatment with cisplatin (DDP) and epirubicin (EPI). Finally, the Kaplan-Meier plotter confirmed that higher expression levels of MEOX2 were related to better overall survival.

CONCLUSION

Our study revealed that the angiogenesis-associated gene MEOX2 can be used as a novel biomarker for breast cancer diagnosis and clinical therapy.

摘要

背景

血管生成在乳腺癌的生长和转移中起关键作用，抑制血管生成已成为癌症治疗的有效策略。我们的研究旨在阐明与乳腺癌血管生成相关的关键候选基因和通路。

方法

从癌症基因组图谱（TCGA）数据库的原始乳腺癌（BRCA）基因数据集中鉴定出差异表达基因（DEG），并对这些DEG进行基因本体分析。随后使用基因表达综合数据库确定枢纽基因。分别通过定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）评估间充质同源盒2（MEOX2）在乳腺癌细胞和组织中的表达。用Kaplan-Meier绘图仪评估MEOX2基因在乳腺癌组织中的预后价值。

结果

在TCGA数据集中共鉴定出61个与血管生成相关的DEG，其中MEOX2基因显著下调。基因本体功能注释和通路富集分析表明，MEOX2在血管发育调控中显著富集。免疫组织化学结果证实，MEOX2在乳腺癌组织中的表达受到抑制，相对较低的水平表明组织血管密集。此外，顺铂（DDP）和表柔比星（EPI）处理后，乳腺癌细胞中MEOX2的表达显著升高。最后，Kaplan-Meier绘图仪证实，MEOX2表达水平较高与更好的总生存率相关。

结论

我们的研究表明，血管生成相关基因MEOX2可作为乳腺癌诊断和临床治疗的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/28f51e4b244b/fonc-12-759300-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/bcb59be5d632/fonc-12-759300-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/bb702744e247/fonc-12-759300-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/794c998cea85/fonc-12-759300-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/32e9c49e97af/fonc-12-759300-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/5b8a62ba98a7/fonc-12-759300-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/28f51e4b244b/fonc-12-759300-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/bcb59be5d632/fonc-12-759300-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/bb702744e247/fonc-12-759300-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/794c998cea85/fonc-12-759300-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/32e9c49e97af/fonc-12-759300-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/5b8a62ba98a7/fonc-12-759300-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6402/9124839/28f51e4b244b/fonc-12-759300-g006.jpg

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