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Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [RNA-Seq]

ABSTRACT: Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using RNA-seq data, we explored changes in the TME and dissected cancer cell intrinsic shapers of the TME.

ORGANISM(S): Mus musculus

PROVIDER: GSE216715 | GEO | 2024/02/22

REPOSITORIES: GEO

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Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [scRNA-Seq]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using scRNA-seq data, we explored changes in the TME to characterize phenotypic differences between immune populations.

2024-02-22 | GSE216805 | GEO

Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using WES data, we explored the tumor mutation frequencies between models and compared them with human datasets.

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Cancer cell genetics shaping of the tumor microenvironmentreveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [WES 2]

Project description:Hepatocellular carcinoma (HCC) is a highly heterogenous disease associated with an equally dynamic tumor microenvironment (TME). We generated somatic HCC mouse models bearing clinically-relevant oncogenic driver combinations that faithfully recapitulated different human HCC subclasses. Using WES data, we explored the tumor mutation frequencies between models and compared them with human datasets.

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Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-22 | GSE216717 | GEO

Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug-resistant gliomas.

Project description: Not available

| S-EPMC9216507 | biostudies-literature

RNA-Seq of primary chronic lymphocytic leukaemia (CLL) tumours treated with anti-IgM antibodies against isotype control treated tumours

Project description:Chronic lymphocytic leukemia (CLL) is a highly heterogenous disease, with vastly diverse phenotypes that cause differing clinical courses ranging from benign disease (requiring no treatment), to a rapidly progressive disease and may require aggressive treatment therapy. Key to the B cell is the B-cell receptor (BCR); CLL utilises the BCR to evade apoptosis and promote proliferation and drug resistance through cross-talk between the TME and through BCR activation. Our experiments engage the BCR to determine downstream impact of BCR stimulation on gene expression in CLL (6 hours after stimulation).

2023-05-01 | E-MTAB-12055 | biostudies-arrayexpress

Human normal and peritumor liver tissues LC-MSMS

Project description:The tumor microenvironment (TME) plays an important role in tumorigenesis1. The TME is usually studied in tumor tissue and in relation to tumor progression2,3, which can limit understanding of how the TME is involved in processes associated with initial tumorigenesis as well as tumor recurrence and metastasis after surgery. To describe the underlying mechanisms of human hepatocellular carcinoma (HCC) occurrence and progression, we propose a new concept, the peritumor microenvironment (PME). We collected normal (all biochemical indicators of liver function, imaging examination and histopathology examination were normal) and peritumor (The liver tissues adjacent to the tumor were approximately 2 cm away from the tumor and were taken from patients with HCC who did not receive tumor radiotherapy, tumor chemotherapy or targeted drug therapy before surgery) to perform a proteomic characterization of the PME in peritumor liver tissues.

2022-02-22 | PXD023118 | Pride

Expression profiles of 30-gene hepatocellular carcinoma molecular classification signature in surgically resected Japanese hepatocellular carcinoma patients

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.

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Human Hepatocellular Carcinoma study

Project description:Global gene expression patterns of 91 human hepatocellular carcinomas (HCC) were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from 18 normal livers were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from human HCC, 20 Î¼g of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with survival of the patients. This association was validated by five independent supervised learning methods. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and anti-apoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification suggesting an etiological involvement of these processes in accelerating the progression of HCC. The biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g. HIF1a) for selective treatment(s) of HCC patients.

2004-10-28 | E-GEOD-1898 | biostudies-arrayexpress

MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a

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

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