ArticleThe Journal of pathology2025
Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues.
Article in The Journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Unraveling lncRNA diversity at a single cell resolution and in a spatial context across different cancer types.Nature methods · 2026Article
- Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence.JHEP reports : innovation in hepatology · 2026Article
- Spatial transcriptomics and histopathological analyses reveal potential biomarkers and immune features linked to recurrence in head and neck cancer.Frontiers in immunology · 2026Article
- Integrating Spatial Omics and Deep Learning: Toward Predictive Models of Cardiomyocyte Differentiation Efficiency.Bioengineering (Basel, Switzerland) · 2025Review
- Long-term fixation impact on archived human nervous tissues for sequencing-based transcriptomics.Brain communications · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues. In this work, we addressed this in a cancer-heterogeneity pipeline, starting with an exploration of the whole transcriptome by two sequencing-based ST protocols capable of measuring coding and non-coding RNAs. We optimised the two protocols to work with challenging formalin-fixed paraffin-embedded (FFPE) tissues, derived from skin. We then assessed alternative imaging methods, including multiplex RNAScope single-molecule imaging and multiplex protein imaging (CODEX). We evaluated the methods' performance for tissues stored from 4 to 14 years ago, covering a range of RNA qualities, allowing us to assess variation. In addition to technical performance metrics, we determined the ability of these methods to quantify tumour heterogeneity. We integrated gene expression profiles with pathological information, charting a new molecular landscape on the pathologically defined tissue regions. Together, this work provides important and comprehensive experimental technical perspectives to consider the applications of ST in deciphering the cancer heterogeneity in archived tissues. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Registered trials
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