背景:体细胞中减数分裂核分裂1(MND1)的异常上调被认为是肿瘤发生的驱动因素之一,而其在乳腺浸润性癌(BRCA)中的表达和作用尚不清楚。因此,这项研究开始了对MND1在各种癌症中的综合评估,并确定了其在BRCA中的作用.
方法:基于公开可用的数据库,包括但不限于UCSCXena,TCGA,GTEx,GEO,STRING,遗传狂躁症,和巨蟹座,我们评估了表达模式,基因组特征,从泛癌症的角度探讨MND1的生物学功能,并探讨MND1在BRCA的预后和治疗中的意义。进行了进一步的分子生物学实验,以确定MND1在增殖中的作用,迁移,BRCA细胞凋亡。
结果:在多种肿瘤类型中观察到MND1水平升高,尤其是在BRCA,COAD,HNSC,LIHC,LUAD,LUSC,STAD,和UCEC。在几种肿瘤中,MND1表达升高与OS缩短显著相关,包括BRCA(HR=1.52[95CI,1.10-2.09],P=0.011)。在外部队列和临床样本中验证了BRCA中MND1的上调。生存分析表明,MND1表达升高与BRCA患者生存率降低相关。鉴定了MND1的共表达基因,随后基于显著相关基因的途径分析表明MND1在DNA复制中起关键作用,细胞周期调节,和DNA损伤修复。观察到MND1的异常升高和激活导致增殖和迁移增加,伴随着BRCA细胞凋亡的减少。
结论:MND1作为各种癌症的诊断和治疗靶向的有希望的生物标志物,包括BRCA。MND1的异常上调和激活与BRCA患者的癌变和不良预后有关。这可能归因于其参与HR依赖性ALT,值得进一步审查。
BACKGROUND: The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA.
METHODS: Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells.
RESULTS: Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells.
CONCLUSIONS: MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny.