Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Shijiazhuang, Hebei, China.
Medicine (Baltimore). 2023 Sep 1;102(35):e34717. doi: 10.1097/MD.0000000000034717.
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.
NUMB 最初被鉴定为一种关键的细胞命运决定因子，通过有丝分裂过程中的不对称分配来调节细胞分化，包括肿瘤细胞。然而，NUMB 及其同源蛋白 NUMBL 参与癌症的机制仍然不清楚。本研究旨在探讨 NUMB 和 NUMBL 在泛癌中的预后意义。在这项研究中，我们使用在线数据库 TIMER2.0、基因表达谱交互式分析、cBioPortal、阿拉巴马大学伯明翰癌症数据分析门户、用于检索相互作用基因/蛋白质的 SearchTool 和 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 的遗传改变集中在子宫体子宫内膜癌中，NUMBL 的更高遗传突变与不同癌症中更长的总生存和无病生存相关。此外，NUMB 肽片段的 S438 位点在 4 种癌症类型中经常被磷酸化，与磷酸化位点相关。此外，内吞作用处理和神经发生调节分别参与了 NUMB 和 NUMBL 的功能机制。此外，通路富集表明 NUMB 参与了 Hippo、神经递质、甲状腺激素和 FoxO 通路，而 MAPK、Hippo、Rap1、mTOR 和 Notch 通路与 NUMBL 的功能相关。本研究强调了 NUMB 和 NUMBL 在泛癌中的预测作用，表明 NUMB 和 NUMBL 可能作为各种恶性肿瘤诊断和预后的潜在标志物。
