MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a
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PROVIDER: PRJNA124713 | ENA |
REPOSITORIES: ENA
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Project description:Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-02-17 | E-GEOD-20596 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC. This SuperSeries is composed of the SubSeries listed below.
2011-02-17 | GSE20596 | GEO
Project description: Not available
| S-EPMC3680790 | biostudies-literature
Project description:The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, a lethal disease lacking specific therapies. This study reports on the identification, characterization, and immunotherapeutic application of HLA-presented neoantigens specific for the DNAJB1-PRKACA fusion transcript in fibrolamellar hepatocellular carcinoma. DNAJB1-PRKACA-derived HLA class I and HLA class II ligands induce multifunctional cytotoxic CD8+ and T-helper 1 CD4+ T cells, and their cellular processing and presentation in DNAJB1-PRKACA expressing tumor cells is demonstrated by mass spectrometry-based immunopeptidome analysis. Single-cell RNA sequencing further identifies multiple T cell receptors from DNAJB1-PRKACA-specific T cells. Vaccination of a fibrolamellar hepatocellular carcinoma patient, suffering from recurrent short interval disease relapses, with DNAJB1-PRKACA-derived peptides under continued Poly (ADP-ribose) polymerase inhibitor therapy induces multifunctional CD4+ T cells, with an activated T-helper 1 phenotype and high T cell receptor clonality. Vaccine-induced DNAJB1-PRKACA-specific T cell responses persist over time and, in contrast to various previous treatments, are accompanied by durable relapse free survival of the patient for more than 21 months post vaccination. Our preclinical and clinical findings identify the DNAJB1-PRKACA protein as source for immunogenic neoepitopes and corresponding T cell receptors and provide efficacy in a single-patient study of T cell-based immunotherapy specifically targeting this oncogenic fusion.
2022-10-13 | PXD029882 | Pride
Project description:Focal gains of VEGFA and molecular classification of hepatocellular carcinoma
| PRJNA103797 | ENA
Project description:Recent advance of RNA-seq technology enabled us to profile the diverse variations of RNA transcripts precisely, including the variants from alternative splicing as well as non-coding transcripts. Here, by performing transcriptome profiling including coding and noncoding transcripts, we identify four molecular subtypes of hepatitis B-related hepatocellular carcinoma (HCC) patients that are characterized by enriched expression of the RNA biotypes of noncoding (NC) and immune-related transcripts (IM) (i.e., IM+NC+, IM-NC+, IM+NC-, IM-NC-). The subtype IM+NC+ shows better prognostic outcome, while the subtype IM+NC- shows the worst prognostic outcome, respectively. Further interrogation of the subtypes identifies long noncoding transcripts (i.e., LINC00844, C3P1, and TRPG1-AS1) as well as an alternatively spliced event of USO1 that play pivotal roles in HCC progression. In addition, we report an oncogenic fusion transcript SLC39A14-PIWIL2 that promotes an aggressive phenotype of HCC. Our comprehensive and systematic analysis of HCC transcriptome identify RNA biotype-based molecular classification, revealing novel driver transcriptome variants that can be potential biomarkers and/or therapeutic targets for precision medicine.
2022-04-01 | GSE113617 | GEO
Project description:To develop a classifier based on microRNAs for primary tumor site identification of liver core biopsies and to explore the influence of surrounding normal liver tissue on classification. Tissue samples from 333 patients, corresponding to one of the following ten assay classes, were obtained from archives of the pathology department, Copenhagen University Hospital, Rigshospitalet, Denmark: Lung cancer, breast cancer, gastric/cardia cancer, colorectal cancer, bladder cancer, pancreatic cancer, hepatocellular carcinoma, cholangiocarcinoma, squamous cell cancers of different origin, and normal liver tissue
2013-10-19 | E-GEOD-51429 | biostudies-arrayexpress
Project description:RNA biotype-associated molecular classification in hepatitis B-related hepatocellular carcinoma
| PRJNA453401 | ENA
Project description:Background & Aims: Hepatocellular carcinoma (HCC) is the second most lethal cancer due to lack of effective therapies. Although promising, HCC molecular classification, which enriches potential responders to specific therapies, has not yet been assessed in clinical trials of anti-HCC drugs. We aimed to overcome these challenges by developing clinicopathological surrogate indices of HCC molecular classification. Methods: HCC classification defined in our previous transcriptome meta-analysis (S1, S2, and S3 subclasses) was implemented in an FDA-approved diagnostic platform (Elements assay, NanoString). Ninety-six HCC tumors (training set) were assayed to develop molecular subclass-predictive indices based on clinicopathological features, which were independently validated in 99 HCC tumors (validation set). Molecular deregulations associated with the histopathological features were determined by pathway analysis. Sample sizes for HCC clinical trials enriched with specific molecular subclasses were determined. Results: HCC subclass-predictive indices were: steatohepatitic (SH)-HCC variant and immune cell infiltrate for S1 subclass, macrotrabecular/compact pattern, lack of pseudoglandular pattern, and high serum alpha-fetoprotein (>400 ng/mL) for S2 subclass, and microtrabecular pattern, lack of SH-HCC and clear cell variants, and lower histological grade for S3 subclass. Macrotrabecular/compact pattern, a predictor of S2 subclass, was associated with activation of therapeutically targetable oncogene YAP and stemness markers EPCAM/KRT19. BMP4 was associated with pseudoglandular pattern. Subclass-predictive indices-based patient enrichment reduced clinical trial sample sizes from 121, 184, and 53 to 30, 43, and 22 for S1, S2, and S3 subclass-targeting therapies, respectively. Conclusions: HCC molecular subclasses can be enriched by clinicopathological indices tightly associated with deregulation of therapeutically targetable molecular pathways.
2015-06-17 | GSE59548 | GEO
Project description:Tumor cells were microdissected from FFPE sections of hepatocellular carcinoma (HCC) samples. Samples were compared between different localisations either within or around the tumor. miRNA was labeled with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit 6 microdissected hepatocellular carcinoma samples were compared to four different tumor localisations (LC: cirrhotic septa of the tumor-adjacent liver; LP: tumor-adjacent liver parenchyma;TC: fibrinous capsule of the tumor; TP: tumor parenchyma)
2015-01-14 | E-GEOD-54537 | biostudies-arrayexpress