MicroRNA- and mRNA-based studies in paraffin-archived human osteosarcoma specimens reveal profiles with reproducible and independent prognostic value
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PROVIDER: PRJNA169852 | ENA |
REPOSITORIES: ENA
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2013-01-22 | GSE39058 | GEO
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2013-01-22 | E-GEOD-39058 | biostudies-arrayexpress
Project description:Profiling histone modifications in clinical archived formalin fixed paraffin embedded samples
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Project description:Triple negative breast tumours from archived formalin fixed paraffin embeded samples of the National Cancer Institute of Mexico were analyzed for differential gene expressión.
2015-05-12 | GSE62502 | GEO
Project description:Background and Aims Formalin-fixed, paraffin-embedded (FFPE) tissue is the most commonly available form of archived clinical specimens, which are often stored as thin sections on glass slides. RNA isolated from such archived section (AS) of FFPE tissue is more degraded compared to freshly cut (FC) FFPE section because of prolonged air exposure. In this study, we evaluated performance of transcriptome profiling-based disease classification in AS-FFPE tissue. Methods Genome-wide gene-expression profiles of AS-FFPE tissues of 83 hepatocellular carcinoma (HCC) and 47 liver cirrhosis samples were generated by using whole-genome DASL assay (Illumina), and compared with the profiles previously produced by using FC tissue sections from the same FFPE blocks. Quality of the profiles and performance of gene signature-based class prediction were systematically evaluated. Results RNA quality and assay reproducibility of AS-FFPE RNA were comparable to intermediate ~ poor quality FC-FFPE samples (R2 as high as 0.93). Gene-expression signal was detected in lower number of probes in AS FFPE samples compared to FC-FFPE samples (proportion of probes with present signal (%P-call): 10%~60% and 70%~90% in AS- and FC-FFPE profiles, respectively). Based on %P-call quality threshold of 20%, 64/88 (77%) HCC and 37/48 (77%) liver profiles were judged as having relatively good quality data with comparable inter-sample correlation. Inter-sample correlation coefficient, as a measure to detect outlier profiles due to poor RNA quality, was also lower in AS-FFPE (0.4~0.9) compared to FC-FFPE (0.6~1.0). In the genome-wide profiling analysis, previously identified molecular subclasses of HCC tumors were reproduced in 67/83 (81%) samples, which was improved to 43/48 (90%) samples when we focused on statistically confident predictions (p<0.05). A 186-gene prognostic signature in liver cirrhosis was reproduced in 32/47 (68%) samples, which was slightly improved to 11/16 (69%) when focused on statistically significant predictions. Conclusions We observed decay of genome-wide transcriptional profiles in AS-FFPE tissues in quantitative manner. However, disease classification was still possible, which suggests potential of AS-FFPE material for clinical diagnosis and prognosis. FFPE tissue sections (10 micron-thick) sliced from 5~16-year-old FFPE blocks and archived for 6~7 years on glass slide Gene-expression profiles of archived section of formalin-fixed paraffin-embedded (AS-FFPE) liver tissues from HCC patients: 47 samples Gene-expression profiles of archived section of formalin-fixed paraffin-embedded (AS-FFPE) tumor tissues from HCC patients: 83 samples
2014-01-31 | E-GEOD-46444 | biostudies-arrayexpress
Project description:Archived tissues are a vast resource of annotated clinical samples. To expand their use for translational studies, we optimized flow sorting and sequencing of single nuclei from archived frozen and FFPE tumor tissues. Our methods, which include isolation and preparation of intact nuclei suitable for library preparations, quality control (QC) metrics for each step, and a single cell sequencing bioinformatic processing and analysis pipeline, were validated with flow sorted nuclei from matching frozen and FFPE ovarian cancer surgical samples and a sequencing panel of 553 amplicons targeting single nucleotide and copy number variants in genes of interest.
2024-06-20 | GSE270364 | GEO
Project description:Here, we present FACT-Seq, a highly sensitive method to decode the histone modifications in FFPE tissues. The FACT-Seq generates the high-quality chromatin profiles from both active and silent histone modifications with 1000 nuclei purified from a single FFPE tissue section, and reveals the disease-specific super enhancers in the FFPE archived human colorectal and human glioblastoma multiforme cancer tissue. In summary, the approach allows decoding the histone modifications that regulate gene expression in archival FFPE tissues with high sensitivity, in order to better understand epigenetic regulation in cancer and precision medicine.
2021-09-03 | GSE171758 | GEO
Project description:Single Nucleus DNA Sequencing of Flow Sorted Archived Frozen and Formalin Fixed Paraffin Embedded Solid Tumors
| PRJNA1119467 | ENA
Project description:Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability.We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity.Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles.Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis supports a possible role of the 14q32 locus in osteosarcoma progression and outcome. Our study creates a paradigm for formalin-fixed, paraffin-embedded-based miRNA biomarker studies in cancer.
| S-EPMC3706900 | biostudies-other
Project description:In recent years, the use of FFPE tissue in gene expression microarray (GEM) studies has become a topic of increased interest, because pathology departments worldwide contain an invaluable source of biological disease-specific FFPE- tissue material. Thus far, some published studies on FFPE tissue consider the processed tissue amenable, whereas other studies assert that the tissue is not useful in GEM. In general, pancreatic tissue is known to contain large amounts of nucleases, leading to high turnover rates and degradation of RNA in the tissue. This characteristic, in combination with FFPE processing time and its effect on the tissue, does not make FFPE pancreatic tissue the obvious choice for GEM. The basis for using FFPE pancreatic tissue in RNA-based assays seems suboptimal. Previous GEM studies have used different FFPE tissue types, but GEM studies on FFPE pancreatic tissue have not been published. In most studies, the tissue was specially processed for use with GEMs. Here we demonstrate the usefulness of randomly archived FFPE pancreatic tissues for GEMs. For this purpose we included FFPE pancreatic tissue from patients with congenital hyperinsulinism or insulinoma; In these patients, pancreas resection is performed when medical treatment is not adequate to prevent hyperinsulinemic hypoglycemia or when patients do not respond to medical treatment. Although ribonuclease-rich, we obtained biologically relevant and disease-specific, significant genes; cancer-related genes and genes involved in a) the regulation of insulin secretion and synthesis, b) amino acid metabolism, and c) calcium ion homeostasis. This application may extend the possibilities of gene expression studies to many tissue types, especially in rare diseases, for which fresh frozen tissue is not readily available. A total of 15 samples were included in this study using a 58K chip. 29,134 human 60mer oligonucleotide targets were arrayed on the chips in duplicates. Each chip is hybridized with sample material (labelled with Cy5) from one patient and reference material (labelled with Cy3). Reference material contains pooled RNA from four different cancer cell lines; HeLa (cervical epithelium), SK-BR-3 (mammary gland), HT29 (colon) and A431 (skin) cells. Seven patients with congenital hyperinsulinism (five FFPE and two frozen samples), one patient with insulinoma and five controls were included in the study. Inclusion criteria for controls was that their cause of death was not pancreas-related. Samples were obtained from archived FFPE pancreatic material. The insulinoma sample was included in the study, because the biopsy was originally divided with one part being frozen and the other part being routinely formalin-fixed and paraffin-embedded. In the study we therefore include a frozen insulinoma sample and a FFPE insulinoma sample that was processed in duplicate.
2012-09-30 | E-GEOD-32610 | biostudies-arrayexpress