Abstract

Simple SummaryNasopharyngeal carcinoma (NPC) is a rare type of head and neck malignant tumor with specific geographical distribution. Growing evidence reveals the dominant roles of cancer stem cells (CSCs) in tumor progression and therapy resistance. However, the heterogeneity of CSCs and potential stemness-related markers for NPC patients are still largely unknown. We undertook a systematical analysis, dissecting the stemness heterogeneity of NPC patients. We classified NPC patients into two optimal clusters based on stemness-related gene lists, which were characterized by distinct clinical outcomes, immune phenotypes, and drug response. The immune cell exclusion is associated with the presence of the NPC stem cell-like phenotype. In particular, novel stemness-related markers including PSMC3IP, NABP2, CDC45, and HJURP were prioritized via WGCNA and Cox regression analysis. Moreover, their stemness traits in NPC cells were verified by Western blot, sphere formation, and CCK8 assays. Our results will provide valuable targets against metastatic or recurrent NPC.Background: Metastasis and recurrence account for the failure of nasopharyngeal carcinoma (NPC) treatment. Growing evidence indicates the dominant roles of cancer stem cells (CSCs) in tumor progression and therapy resistance. However, the heterogeneity of CSCs and potential stemness-related markers in NPC patients are still largely unknown. Methods: Consensus clustering was first applied to identify robust stemness subtypes for NPC patients based on the activities of stem cell gene sets. The differences in clinical outcomes, tumor immune microenvironment (TIME), and drug response were compared between subtypes. The stemness-related markers were prioritized via weighted gene correlation network analysis (WGCNA) and Cox regression, and verified through in vitro experiments. Results: NPC patients were classified int