Comprehensive pan-cancer analysis of expression profiles and prognostic significance for NUMB and NUMBL in human tumors.

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.