Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Departments of Burn and Plastic, Ningxiang People's Hospital, Hunan University of Chinese Medicine, Changsha, 410600, Hunan, China.
Sci Rep. 2023 Mar 17;13(1):4435. doi: 10.1038/s41598-023-31109-6.
BRCA1 interacting helicase 1 (BRIP1) alteration was crucial in tumors and it was a potential therapeutic target in ovarian serous cystadenocarcinoma (OV). Although a small number of studies had focused on BRIP1, an extensive study of BRIP1 genetic mutation and its clinical application in different cancer types had not been analyzed. In the current study, we analyzed BRIP1 abnormal expression, methylation, mutation, and their clinical application via several extensive datasets, which covered over 10,000 tumor samples across more than 30 cancer types. The total mutation rate of BRIP1 was rare in pan cancer. Its alteration frequency, oncogenic effects, mutation, and therapeutic implications were different in each cancer. 242 BRIP1 mutations were found across 32 cancer types. UCEC had the highest alteration (mutation and CNV) frequency. In addition, BRIP1 was a crucial oncogenic factor in OV and BRCA. BRIP1 mutation in PRAD was targetable, and FDA had approved a new drug. Moreover, Kaplan-Meier curve analysis showed that BRIP1 expression and genetic aberrations were closely related to patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. The current study profiled the total BRIP1 mutation spectrum and offered an extensive molecular outlook of BRIP1 in a pan cancer analysis. And it suggested a brand-new perspective for clinical cancer therapy.
BRCA1 相互作用解旋酶 1(BRIP1)改变在肿瘤中至关重要,是卵巢浆液性囊腺癌(OV)的潜在治疗靶点。尽管少数研究集中在 BRIP1 上,但尚未分析 BRIP1 基因突变及其在不同癌症类型中的广泛临床应用。在本研究中,我们通过涵盖超过 30 种癌症类型的超过 10,000 个肿瘤样本的多个广泛数据集,分析了 BRIP1 的异常表达、甲基化、突变及其临床应用。BRIP1 在泛癌中的总突变率罕见。其改变频率、致癌效应、突变和治疗意义在每种癌症中均不同。在 32 种癌症类型中发现了 242 个 BRIP1 突变。UCEC 具有最高的改变(突变和 CNV)频率。此外,BRIP1 是 OV 和 BRCA 中的关键致癌因素。PRAD 中的 BRIP1 突变是可靶向的,FDA 已批准一种新药。此外,Kaplan-Meier 曲线分析表明,BRIP1 的表达和遗传异常与几种癌症患者的生存密切相关,表明它们有潜力作为新的肿瘤标志物和治疗靶点。本研究描绘了 BRIP1 的总突变谱,并在泛癌分析中提供了 BRIP1 的广泛分子观点。并为临床癌症治疗提供了全新的视角。