Background. Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis‐related processes. However, the prognostic significance of m6A‐related lncRNAs and their associations with stemness in low‐grade glioma (LGG) remain to be clarified. Methods. A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A‐related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A‐related lncRNAs was constructed and validated in external LGG datasets. Results. Based on the expression of LINC02984, PFKP‐DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions. This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.

DNA methylation has shown great potential in Alzheimer’s disease (AD) blood diagnosis. However, the ability of long non-coding RNAs (lncRNAs), which

Breast cancer (BRCA) is a highly heterogeneous malignancy comprising multiple molecular subtypes with distinct transcriptional and clinical characteristics

Human papillomavirus (HPV) infection plays a significant role in shaping the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC). However, the heterogeneity of cellular states and ecosystems within the tumor microenvironment of HPV-infected HNSCC is still largely unknown. Using the EcoTyper framework, we perform an extensive evaluation of HPV-related cellular profiles and cellular ecotypes (CEs) in HNSCC. Single-cell RNA sequencing reveals 46 unique states across 12 principal cell types. Spatial transcriptomics confirm the spatial correlation of cellular states from the same ecotype. Moreover, prognostic and drug sensitivity analyses reveal the clinically relevant and therapeutic vulnerabilities of cellular status for patients with different HPV statuses. In conclusion, our findings provide insights into the different cellular organizations and microenvironments of HPV-related HNSCC, with potential implications for the development of biomarkers and precision therapies.

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 into C1 and C2 subtypes. The C2 subtype exhibited higher activities of stem cell gene sets, worse prognosis, and aggressive tumor progression thus defined as stem cell-like tumor phenotype. The exclusionary relationships between tumor stemness and TIME infiltration were observed. The efficacy of several drugs and immunotherapy varied between NPC stemness subtypes. Through the WGCNA and survival analysis, we found that PSMC3IP, NABP2, CDC45, and HJURP were stemness-relevant genes. Sphere formation assays and analysis of the protein expression of stem cell markers by Western blotting revealed the roles of PSMC3IP, NABP2, CDC45, and HJURP in promoting CSC properties. Moreover, these genes were found to be related to the therapeutic effect of telomerase inhibitor in CCK8 experiments. Conclusions: This study systematically characterized two NPC subtypes with distinct stemness features, clinical outcomes, and TIME features. Novel stemness-related markers will provide valuable targets against metastatic or recurrent NPC.