ArticleNucleic acids research2020
Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 34 citations in OpenAlex.
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
- The Expression Profiles of lncRNAs Are Associated with Neoadjuvant Chemotherapy Resistance in Locally Advanced, Luminal B-Type Breast Cancer.International journal of molecular sciences · 2024Article
- Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology · 2024Review
- Recent Advances in High-sensitivityActa histochemica et cytochemica · 2023Review
- Automated annotations of epithelial cells and stroma in hematoxylin-eosin-stained whole-slide images using cytokeratin re-staining.The journal of pathology. Clinical research · 2022Article
- A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology.Frontiers in immunology · 2022Review
- Single-Cell RNA Sequencing Reveals Endothelial Cell Transcriptome Heterogeneity Under Homeostatic Laminar Flow.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Review
- Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.PloS one · 2021Article
- Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise.Cancers · 2020Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiplexed RNA in situ hybridization for the analysis of gene expression patterns plays an important role in investigating development and disease. Here, we present a method for multiplexed RNA-ISH to detect spatial tumor heterogeneity in tissue sections. We made use of a microfluidic chip to deliver ISH-probes locally to regions of a few hundred micrometers over time periods of tens of minutes. This spatial multiplexing method can be combined with ISH-approaches based on signal amplification, with bright field detection and with the commonly used format of formalin-fixed paraffin-embedded tissue sections. By using this method, we analyzed the expression of HER2 with internal positive and negative controls (ActB, dapB) as well as predictive biomarker panels (ER, PgR, HER2) in a spatially multiplexed manner on single mammary carcinoma sections. We further demonstrated the applicability of the technique for subtype differentiation in breast cancer. Local analysis of HER2 revealed medium to high spatial heterogeneity of gene expression (Cohen effect size r = 0.4) in equivocally tested tumor tissues. Thereby, we exemplify the importance of using such a complementary approach for the analysis of spatial heterogeneity, in particular for equivocally tested tumor samples. As the method is compatible with a range of ISH approaches and tissue samples, it has the potential to find broad applicability in the context of molecular analysis of human diseases.
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