Lyu Lijuan, Wang Meng, Zheng Yi, Tian Tian, Deng Yujiao, Xu Peng, Lin Shuai, Yang Si, Zhou Linghui, Hao Qian, Wu Ying, Dai Zhijun, Kang Huafeng
Department of Oncology, The 2nd Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, People's Republic of China.
Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, People's Republic of China.
Cancer Manag Res. 2020 Dec 3;12:12457-12471. doi: 10.2147/CMAR.S280009. eCollection 2020.
Family with sequence similarity 234 member B (), a protein-coding gene, is mainly expressed in brain tissues. Its clinical significance and biological function in tumors, especially in breast cancer (BC), have not been elucidated.
We firstly investigated the expression pattern of at the mRNA and protein levels using Oncomine, TCGA portal, GEPIA, TIMER, HPA, and UALCAN databases, then applied bc-GenExMiner to assess the associations between expression level of and clinicopathological features of BC. Besides, we also verified the expression of expression in clinical BC samples using qRT-PCR. Subsequently, GEPIA, bc-GenExMiner, and TIMER databases were used to analyze the prognostic significance of in all BC and different molecular subtypes. Finally, we conducted co-expression analysis and gene set enrichment analysis (GSEA). Additionally, we explored the regulatory mechanism of in BC.
Both bioinformatics analysis and experimental verification confirmed that the expression was significantly higher at the mRNA and protein levels in luminal BC tissues than in adjacent normal tissues. High expression was significantly correlated with older age, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor 2-negative, wild-type p53, low Nottingham prognostic index, low Scarff-Bloom-Richardson grade, lymph node metastasis positivity, and high tumor stage. Moreover, survival analysis indicated that high expression was significantly related to a worse prognosis in patients with luminal BC. GSEA indicated that was positively related to membrane transport process and negatively associated with immune response function. Besides, mechanism exploration indicated that pseudogene might act as endogenous RNA to compete with or for binding to , thereby upregulating the expression of in luminal BC.
Our results suggest that may be a candidate therapeutic target or prognostic marker for luminal breast cancer.
序列相似性家族234成员B(FAM234B)是一种蛋白质编码基因,主要在脑组织中表达。其在肿瘤尤其是乳腺癌(BC)中的临床意义和生物学功能尚未阐明。
我们首先使用Oncomine、TCGA数据库、GEPIA、TIMER、HPA和UALCAN数据库研究FAM234B在mRNA和蛋白质水平的表达模式,然后应用bc-GenExMiner评估FAM234B表达水平与BC临床病理特征之间的关联。此外,我们还使用qRT-PCR验证了FAM234B在临床BC样本中的表达。随后,利用GEPIA、bc-GenExMiner和TIMER数据库分析FAM234B在所有BC及不同分子亚型中的预后意义。最后,我们进行了共表达分析和基因集富集分析(GSEA)。此外,我们还探讨了FAM234B在BC中的调控机制。
生物信息学分析和实验验证均证实,管腔型BC组织中FAM234B的mRNA和蛋白质水平表达明显高于相邻正常组织。FAM234B高表达与年龄较大、雌激素受体阳性、孕激素受体阳性、人表皮生长因子受体2阴性、野生型p53、低诺丁汉预后指数、低斯卡夫-布卢姆-理查森分级、淋巴结转移阳性和高肿瘤分期显著相关。此外,生存分析表明,FAM234B高表达与管腔型BC患者的预后较差显著相关。GSEA表明,FAM234B与膜转运过程呈正相关,与免疫反应功能呈负相关。此外,机制探索表明,假基因FAM234B-AS1可能作为内源性RNA与miR-197-3p或miR-429竞争结合AGO2,从而上调管腔型BC中FAM234B的表达。
我们的结果表明,FAM234B可能是管腔型乳腺癌的候选治疗靶点或预后标志物。