NUMB被最初鉴定为一个关键的细胞命运决定因子，通过不对称分裂调控细胞分化，包括肿瘤细胞。然而，对于NUMB及其同源蛋白NUMBLIKE (NUMBL)在癌症中参与机制的系统评估尚未有报道。本研究旨在调查NUMB和NUMBL在全癌中的预后意义。在本研究中，我们使用了在线数据库TIMER2.0、基因表达分析交互式分析、cBioPortal、University of ALabama at Birmingham癌症数据分析门户、SearchTool for the Retrieval of Interacting Genes/Proteins以及R软件，重点研究了NUMB/NUMBL与肿瘤发生、进展、突变、磷酸化、功能和预后之间的相关性。本研究表明，NUMB和NUMBL的异常表达与临床病理分期和生存预后显著相关。此外，NUMB和NUMBL的基因变异主要集中在子宫体内膜癌，并且NUMBL的较高基因突变与不同癌症中更长的总生存期和无病生存期相关。此外，NUMB肽段的S438位点在4种癌症类型中经常磷酸化，并与其磷酸化位点相关。此外，内吞作用和神经发生调控分别参与了NUMB和NUMBL的功能机制。此外，途径富集分析显示NUMB与Hippo、神经营养因子、甲状腺激素和FoxO途径有关，而MAPK、Hippo、Rap1、mTOR和Notch途径与NUMBL的功能相关。本研究强调了NUMB和NUMBL在全癌中的预测角色，并提出NUMB和NUMBL可能作为各种恶性肿瘤的潜在诊断和预后标志物。Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

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.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.