Transcriptome profiling of Benign and Malignant Pancreatic Headmass
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE143754 | GEO | 2020/11/12
REPOSITORIES: GEO
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Project description:Transcriptome profiling of Benign and Malignant Pancreatic Headmass
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Project description:Intra-tumor heterogeneity (ITH) has been studied at the morphologic, genomic, and transcriptomic level, but not proteomic level. Recent advances in mass spectrometric (MS) proteome quantification techniques, exemplified by SWATH-MS, a massively parallel targeting method, now also support precise quantitative proteomic comparisons across multiple samples, thus identifying molecular and implied functional differences. Here we used SWATH-MS to analyze the proteome profiles of a set of fresh-frozen prostate tissue samples derived from radical prostatectomy specimens. A high confidence set of 1,906 proteins were consistently quantified across 60 biopsy-level tissue samples from three prostatectomy patients, each consisting of 1.0 mm punch biopsies from histologically malignant (acinar and ductal adenocarcinoma) and matching benign prostatic hyperplasia tissues. The quantitative protein profiles allowed independent quantification of the degree of intra-tumor heterogeneity for each protein in benign and malignant tissues. We found that while majority of the proteins showed comparably low intra-tumor variability, 122 proteins were highly variable in malignant and/or matching benign tissues. We observed that proteins that varied between patients or tissue types also tended to be highly variable within prostate tissues, suggesting that these variability patterns will be a critical selection criterion in future protein biomarker studies. The data also permitted investigation of the heterogeneity of multiple biochemical pathways. The high variability of several of the pathways, including Glypican-1 network, alpha-linolenic acid metabolism and celecoxib pathway, explained contradictory results regarding them in the literature. In conclusion, we demonstrated a methodology for investigating proteomic intra-tumor heterogeneity from biopsy-level tissue samples, and quantified the degree of intra-tumor heterogeneity of 1,906 proteins in prostate tumors. The method and data presented here have advanced our understanding of tumor biology and offered critical insights for future biomarker development.
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Project description:Salivary gland myoepithelial tumors are relatively uncommon tumors with an unpredictable clinical course. More knowledge about their genetic profiles is necessary to identify novel predictors of disease. In this study, we subjected 27 primary tumors (15 myoepitheliomas and 12 myoepithelial carcinomas) to genome-wide microarray-based comparative genomic hybridization (array CGH). We set out to delineate known chromosomal aberrations in more detail and to unravel chromosomal differences between benign myoepitheliomas and myoepithelial carcinomas. Patterns of DNA copy number aberrations were analyzed by unsupervised hierarchical cluster analysis. Both benign and malignant tumors revealed a limited amount of chromosomal alterations (median of 5 and 7.5 respectively). In both tumor groups, high frequency gains (≥20%) were found mainly at loci of growth factors and growth factor receptors (e.g. PDGF, FGF(R)s, and EGFR). In myoepitheliomas, high frequency losses (≥20%) were detected at regions of proto-cadherins. Cluster analysis of the array CGH data identified three clusters. Differential copy numbers on chromosome arm 8q and chromosome 17 set the clusters apart. Cluster 1 contained a mixture of the two phenotypes (n=10), cluster 2 included mostly benign tumors (n=10), and cluster 3 only contained carcinomas (n=7). Supervised analysis between malignant and benign tumors revealed a 36 Mbp-region at 8q being more frequently gained in malignant tumors (p=0.007, FDR=0.05). This is the first study investigating genomic differences between benign and malignant myoepithelial tumors of the salivary glands at a genomic level. Both unsupervised and supervised analysis of the genomic profiles revealed chromosome arm 8q to be involved in the malignant phenotype of salivary gland myoepitheliomas.
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