Frozen tissue coring and layered histological analysis improves cell type-specific proteogenomic characterization of pancreatic adenocarcinoma.

Autor: Savage SR; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA. ssavage@bcm.edu.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. ssavage@bcm.edu., Wang Y; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA., Chen L; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA., Jewell S; Van Andel Institute, Grand Rapids, MI, 49503, USA., Newton C; Van Andel Institute, Grand Rapids, MI, 49503, USA., Dou Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Li QK; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA., Bathe OF; Departments of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Arnie Charbonneau Cancer Institute, Calgary, AB, Canada., Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD, 20850, USA., Omenn GS; Department of Computational Medicine & Bioinformatics, Internal Medicine, Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA., Thiagarajan M; Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA., Zhang H; Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA., Hostetter G; Van Andel Institute, Grand Rapids, MI, 49503, USA., Zhang B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
Jazyk: angličtina
Zdroj: Clinical proteomics [Clin Proteomics] 2024 Jan 30; Vol. 21 (1), pp. 7. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1186/s12014-024-09450-3
Abstrakt: Background: Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses.
Methods: We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular and histology data.
Results: Tissue cores had mixed cell composition at varying depths throughout. Average cell type percentages assessed by histology throughout the core were better associated with KRAS variant allele frequencies than standard histology assessment of the cut surface. Clustering based on serial histology data separated the cores into three groups with enrichment of neoplastic epithelium, stroma, and acinar cells, respectively. Using this classification, tumor overexpressed proteins identified in bulk tissue analysis were assigned into epithelial- or stroma-specific categories, which revealed novel epithelial-specific tumor overexpressed proteins.
Conclusions: Our study demonstrates the feasibility of multi-omics data generation from tissue cores, the necessity of interval H&E stains in serial histology sections, and the utility of coring to improve analysis over bulk tissue data.
(© 2024. The Author(s).)
Databáze: MEDLINE
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