GEO series

Epigenetic Subtypes of High-Grade T1 Bladder Cancer Reveal Intra-Tumor Heterogeneity and Distinct Interactions with Tumor Microenvironment

GSE281743 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 41 samples Submitted 2026/06/10 Platform GPL24676Platform GPL34284

Summary

High-Grade T1 (HGT1) Non-Muscle Invasive Bladder Cancer (NMIBC) is a clinically heterogeneous disease, characterized by unpredictable treatment responses and limited tools for recurrence prediction. Although molecular classification efforts have been made, patient stratification still primarily relies on clinicopathological features, which offer limited clinical precision. In this study, we integrated chromatin profiling in bulk with single-nuclei(sn) RNA-seq, immunohistochemistry and spatial transcriptomics to define epigenetic subtypes of HGT1, characterize their heterogeneity, and investigate tumor–microenvironment interactions. Our findings reveal distinct chromatin profiles differentiating urothelial (URO) and micropapillary (MP) histological variants of high-risk HGT1. We identified three epigenetic states: two within the URO group, luminal-like inflammatory (LLI) and basal-like (BL), and a separate signature unique to MP tumors. Single-cell and spatial resolution approaches validated intratumoral heterogeneity and provided insight into subtype-specific microenvironmental contexts. Notably, ∼40% of URO tumors exhibited spatially distinct coexisting LLI and BL components. BL regions showed enrichment for angiogenesis and hypoxia pathways and were preferentially located near vascular stroma, while LLI regions showed to be located at the core of the tumor. MP tumors featured a markedly different microenvironment, characterized by diverse populations of cancer-associated fibroblasts (CAFs) and M2-polarized macrophages intermingled with tumor cells, suggesting a more immunosuppressive niche which could account for their worse clinical outcome. URO tumors, by comparison, showed a more immune-excluded phenotype. These findings provide a detailed molecular and spatial map of bladder cancer heterogeneity, highlighting how distinct epigenetic subtypes and histological variants are associated with tumor architecture and microenvironmental interactions. Our data underscore the need for subtype-specific therapeutic strategies to more effectively address the complexity already existing at HGT1 bladder cancer.

Published in

Epigenetic subtypes of high-grade T1 bladder cancer reveal intra-tumor heterogeneity and distinct interactions with tumor microenvironment

Bellmunt J, Xie Y, Juanpere N et al. · Theranostics 2026 · PMID 42244999 · doi:10.7150/thno.129729

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Direct links to NCBI, no account and no request form: the whole study as GSE281743_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 41 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1185647 and SRA study SRP544911. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42244999) ↗

Study design

25 conditions, each sampled once — no replicated groups

ucc ×11 MP ×6

Read from the first 40 of 41 sample titles: 25 distinct titles with little repetition. Check it against the sample list below before relying on it.

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