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Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma

ABSTRACT: Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features. Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes. Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179443 | GEO | 2022/07/12

REPOSITORIES: GEO

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Project description:The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. Dendritic cells (DC) were purified from the blood of healthy human donors. Each replicate comes from a different donor. There are 6 freshly purified samples (Control_0h), 4 DC samples cultured during 6h with no additional stimulus than the medium (Control_6h), 5 samples cultured during 6h with recombinant TSLP (Thymic Stromal Lymphopoietin at 20 ng/uL) (TSLP_6h) and 3 samples cultured during 6h with recombinant TNF (Tumor necrosis factor at 20 ng/mL) (TNF_6h).

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Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma

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