Zhu Lizhe, Yu Shibo, Jiang Siyuan, Ge Guanqun, Yan Yu, Zhou Yuhui, Niu Ligang, He Jianjun, Ren Yu, Wang Bin
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
PeerJ. 2020 Nov 20;8:e10421. doi: 10.7717/peerj.10421. eCollection 2020.
The homeobox gene family, encoding a specific nuclear protein, is essential for embryonic development, differentiation, and homeostasis. The role of the HOXB3 protein varies in different tumors. This study aims to explore the role of the HOXB3 gene in breast cancer.
Differentially expressed genes were screened by analyzing metastatic breast cancer gene chip data from TCGA and GEO databases. The function of the selected HOXB3 gene was also analyzed in different databases and through molecular biology methods, such as qRT-PCR, western blot and IF to verify bioinformatics findings.
Both bioinformatics analyses and western blot showed that HOXB3 was lost in breast cancer compared to normal breast tissue. Survival analysis also showed that lower expression of HOXB3 was associated with poor prognosis. Bioinformatics analyses further showed that HOXB3 was positively correlated with hormone receptors. Metascape for GO analysis of GEO data provided possible mechanisms that HOXB3 could positively regulate cell adhesion, inhibit cell proliferation and activate immune response in breast cancer; moreover, GSEA included several cancer-associated pathways.
In summary, HOXB3 expression was decreased in breast cancer, and it was associated with poor prognosis. It might become a new biomarker to predict prognosis of breast cancer.
同源框基因家族编码一种特定的核蛋白，对胚胎发育、分化和体内平衡至关重要。HOXB3蛋白在不同肿瘤中的作用各不相同。本研究旨在探讨HOXB3基因在乳腺癌中的作用。
通过分析来自TCGA和GEO数据库的转移性乳腺癌基因芯片数据筛选差异表达基因。还在不同数据库中并通过分子生物学方法（如qRT-PCR、蛋白质免疫印迹和免疫荧光）分析所选HOXB3基因的功能，以验证生物信息学研究结果。
生物信息学分析和蛋白质免疫印迹均显示，与正常乳腺组织相比，HOXB3在乳腺癌中缺失。生存分析还显示，HOXB3低表达与预后不良相关。生物信息学分析进一步表明，HOXB3与激素受体呈正相关。对GEO数据进行GO分析的Metascape提供了HOXB3可能在乳腺癌中正向调节细胞黏附、抑制细胞增殖并激活免疫反应的潜在机制；此外，基因集富集分析（GSEA）包括几个与癌症相关的通路。
综上所述，HOXB3在乳腺癌中表达降低，且与预后不良相关。它可能成为预测乳腺癌预后的一种新生物标志物。
