An integrated, transcript-resolution atlas of prostate cancer progression unmasks associations with oncogenic pathways
Abstract
Summary: Most genes produce multiple non-coding and coding RNA transcripts with potentially divergent biological functions, yet their contribution to cancer remains largely unexplored. Here, we built an integrated, transcript-resolution RNA-sequencing atlas of prostate cancer spanning 1,140 clinical samples from 10 independent studies, covering the full range of disease progression from normal tissue to primary, hormone-sensitive, and castration-resistant disease. Cross-study integration removes technical batch effects while retaining the biological heterogeneity that distinguishes these disease states, a property we validate against long-read sequencing and leverage to place newly incorporated external cohorts within this disease-progression context. We describe transcript patterns of oncogenic and tumor-suppressive long non-coding RNAs along disease progression and identify 41 protein-coding genes with significant isoform switches in cancer-relevant pathways, including WNT2B, RNF43, RELA, BRCA1, ROCK2, and TRIM11. Finally, we provide the Prostate Cancer Atlas ( www.prostatecanceratlas.org ), an interactive web resource that lets researchers contextualize their own transcriptomic data against this atlas.
Highlights: ● Data reprocessing removes batch effects and preserves prostate cancer heterogeneity ● Atlas maps lncRNA transcript changes along disease progression ● Isoform switches reveal domain-specific roles in tumor suppressors and oncogenes ● A public web tool…
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