PDF(Pubmed)
Abstract：
NUMB has been initially identified as a critical cell fate determinant that modulates cell differentiation via asymmetrical partitioning during mitosis, including tumor cells. However, it remains absent that a systematic assessment of the mechanisms underlying NUMB and its homologous protein NUMBLIKE (NUMBL) involvement in cancer. This study aimed to investigate the prognostic significance for NUMB and NUMBL in pan-cancer. In this study, using the online databases TIMER2.0, gene expression profiling interactive analysis, cBioPortal, the University of ALabama at Birmingham CANcer data analysis Portal, SearchTool for the Retrieval of Interacting Genes/Proteins, and R software, we focused on the relevance between NUMB/NUMBL and oncogenesis, progression, mutation, phosphorylation, function and prognosis. This study demonstrated that abnormal expression of NUMB and NUMBL were found to be significantly associated with clinicopathologic stages and the prognosis of survival. Besides, genetic alternations of NUMB and NUMBL focused on uterine corpus endometrial carcinoma, and higher genetic mutations of NUMBL were correlated with more prolonged overall survival and disease-free survival in different cancers. Moreover, S438 locus of NUMB peptide fragment was frequently phosphorylated in 4 cancer types and relevant to its phosphorylation sites. Furthermore, endocytosis processing and neurogenesis regulation were involved in the functional mechanisms of NUMB and NUMBL separately. Additionally, the pathway enrichment suggested that NUMB was implicated in Hippo, Neurotrophin, Thyroid hormone, and FoxO pathways, while MAPK, Hippo, Rap1, mTOR, and Notch pathways were related to the functions of NUMBL. This study highlights the predictive roles of NUMB and NUMBL in pan-cancer, suggesting NUMB and NUMBL might be served as potential biomarkers for diagnosis and prognosis in various malignant tumors.
摘要：
NUMB最初被认为是通过有丝分裂过程中的不对称分配来调节细胞分化的关键细胞命运决定因素。包括肿瘤细胞.然而,目前尚没有对NUMB及其同源蛋白NUMBL(NUMBL)参与癌症的潜在机制进行系统评估.本研究旨在探讨NUMB和NUMBL在泛癌症中的预后意义。在这项研究中,使用在线数据库TIMER2.0，基因表达谱交互式分析，cBioPortal,阿拉巴马大学伯明翰CANcer数据分析门户，检索相互作用基因/蛋白质的搜索工具，和R软件，我们专注于NUMB/NUMBL与肿瘤发生之间的相关性，programming,突变,磷酸化,功能和预后。这项研究表明，NUMB和NUMBL的异常表达与临床病理分期和生存预后显着相关。此外,NUMB和NUMBL的遗传交替集中在子宫内膜癌，在不同的癌症中,更高的NUMBL基因突变与更长的总生存期和无病生存期相关.此外，NUMB肽片段的S438位点在4种癌症类型中经常被磷酸化并且与其磷酸化位点相关。此外，内吞加工和神经发生调节分别参与NUMB和NUMBL的功能机制。此外,途径富集表明NUMB与河马有关，神经营养蛋白,甲状腺激素,和FoxO途径，而MAPK,河马,Rap1,mTOR,Notch通路与NUMBL的功能有关。这项研究强调了NUMB和NUMBL在泛癌症中的预测作用，提示NUMB和NUMBL可能是各种恶性肿瘤诊断和预后的潜在生物标志物。
