دورية أكاديمية
Topographic analysis of pancreatic cancer by TMA and digital spatial profiling reveals biological complexity with potential therapeutic implications
| العنوان: | Topographic analysis of pancreatic cancer by TMA and digital spatial profiling reveals biological complexity with potential therapeutic implications |
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| المؤلفون: | Victoria Bingham, Louise Harewood, Stephen McQuaid, Stephanie G. Craig, Julia F. Revolta, Chang S. Kim, Shambhavi Srivastava, Javier Quezada-Marín, Matthew P. Humphries, Manuel Salto-Tellez |
| المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-14 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Pancreatic ductal adenocarcinoma, Topographic tissue microarrays, Image analysis, Biomarkers, Tumour heterogeneity, Digital spatial profiling, Medicine, Science |
| الوصف: | Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human malignancies. Tissue microarrays (TMA) are an established method of high throughput biomarker interrogation in tissues but may not capture histological features of cancer with potential biological relevance. Topographic TMAs (T-TMAs) representing pathophysiological hallmarks of cancer were constructed from representative, retrospective PDAC diagnostic material, including 72 individual core tissue samples. The T-TMA was interrogated with tissue hybridization-based experiments to confirm the accuracy of the topographic sampling, expression of pro-tumourigenic and immune mediators of cancer, totalling more than 750 individual biomarker analyses. A custom designed Next Generation Sequencing (NGS) panel and a spatial distribution-specific transcriptomic evaluation were also employed. The morphological choice of the pathophysiological hallmarks of cancer was confirmed by protein-specific expression. Quantitative analysis identified topography-specific patterns of expression in the IDO/TGF-β axis; with a heterogeneous relationship of inflammation and desmoplasia across hallmark areas and a general but variable protein and gene expression of c-MET. NGS results highlighted underlying genetic heterogeneity within samples, which may have a confounding influence on the expression of a particular biomarker. T-TMAs, integrated with quantitative biomarker digital scoring, are useful tools to identify hallmark specific expression of biomarkers in pancreatic cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-62031-0 |
| URL الوصول: | https://doaj.org/article/d25a41f56be2446d9bbeea882fd613c5 |
| رقم الأكسشن: | edsdoj.25a41f56be2446d9bbeea882fd613c5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-62031-0 |