Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

Modeling nervous system tumors with human stem cells and organoids

Nervous system cancers are the 10th leading cause of death worldwide,many of which are difficult to diagnose and exhibit varying degrees of treatment resistance.The limitations of existing cancer models,such as patient-derived xenograft(PDX)models and genetically engineered mouse(GEM)models,call for the development of novel preclinical cancer models to more faithfully mimic the patient’s cancer and offer additional insights.Recent advances in human stem cell biology,organoid,and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models:cell-of-origin models,tumor organoids,and 3D multicellular coculture models.In this review,we introduced and compared different human stem cell/organoid-derived models,and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems,including glioblastoma(GBM),H3K27M-mutant Diffuse Midline Glioma(DMG)and H3G34R-mutant High-grade Glioma(HGG),Low-grade Glioma(LGG),Neurofibromatosis Type 1(NF1),Neurofibromatosis Type 2(NF2),Medulloblastoma(MB),Atypical Teratoid/rhabdoid Tumor(AT/RT),and meningioma.We further compared these models with PDX and GEM models,and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.