Mongre Raj Kumar, Mishra Chandra Bhushan, Jung Samil, Lee Beom Suk, Quynh Nguyen Thi Ngoc, Anh Nguyen Hai, Myagmarjav Davaajragal, Jo Taeyeon, Lee Myeong-Sok
Molecular Cancer Biology Laboratory, Cellular Heterogeneity Research Center, Department of Biosystem, Sookmyung Women's University, Hyochangwon gil-52, Yongsan-Gu, Seoul 140-742, Republic of Korea.
College of Pharmacy, Sookmyung Women's University, Hyochangwon gil-52, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Mol Ther Oncolytics. 2020 Sep 16;19:105-126. doi: 10.1016/j.omto.2020.09.003. eCollection 2020 Dec 16.
TRIP-Brs, a group of transcription factors (TFs) that modulate several mechanisms in higher organisms. However, the novel paradigm to target TRIP-Brs in specific cancer remains to be deciphered. In particular, comprehensive analysis of TRIP-Brs in clinicopathological and patients' prognosis, especially in breast cancer (BRCA), is being greatly ignored. Therefore, we explored the key roles of TRIP-Br expression, modulatory effects, mutations, immune infiltration, and prognosis in BRCA using multidimensional approaches. We found elevated levels of TRIP-Brs in numerous cancer tissues than normal. Higher expression of TRIP-Br-2/4/5 was shown to be positively associated with lower survival, tumor grade, and malignancy of patients with BRCA. Additionally, higher TRIP-Br-3/4 were also significantly linked with worse/short survival of BRCA patients. TRIP-Br-1/4/5 were significantly overexpressed and enhanced tumorigenesis in large-scale BRCA datasets. The mRNA levels of TRIP-Brs have been also correlated with tumor immune infiltrate in BRCA patients. In addition, TRIP-Brs synergistically play a pivotal role in central carbon metabolism, cancer-associated pathways, cell cycle, and thyroid hormone signaling, which evoke that TRIP-Brs may be a potential target for the therapy of BRCA. Thus, this investigation may lay a foundation for further research on TRIP-Br-mediated management of BRCA.
TRIP-Brs是一组转录因子,可调节高等生物中的多种机制。然而,在特定癌症中靶向TRIP-Brs的新范例仍有待破解。特别是,TRIP-Brs在临床病理和患者预后方面的综合分析,尤其是在乳腺癌(BRCA)中,一直被严重忽视。因此,我们使用多维方法探讨了TRIP-Br表达、调节作用、突变、免疫浸润和预后在BRCA中的关键作用。我们发现,与正常组织相比,许多癌症组织中TRIP-Brs的水平升高。TRIP-Br-2/4/5的高表达与BRCA患者的低生存率、肿瘤分级和恶性程度呈正相关。此外,较高的TRIP-Br-3/4也与BRCA患者较差/较短的生存期显著相关。在大规模BRCA数据集中,TRIP-Br-1/4/5显著过表达并增强了肿瘤发生。TRIP-Brs的mRNA水平也与BRCA患者的肿瘤免疫浸润相关。此外,TRIP-Brs在中心碳代谢、癌症相关途径、细胞周期和甲状腺激素信号传导中协同发挥关键作用,这表明TRIP-Brs可能是BRCA治疗的潜在靶点。因此,本研究可能为进一步研究TRIP-Br介导的BRCA管理奠定基础。