Human liver single nucleus and single cell RNA sequencing identify a hepatocellular carcinoma-associated cell-type affecting survival

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: May 17, 2022

Abstract Background Hepatocellular carcinoma (HCC) is a common primary liver cancer with poor overall survival. We hypothesized that there are HCC-associated cell-types impact patient Methods combined single nucleus (snRNA-seq), cell (scRNA-seq), and bulk RNA-sequencing (RNA-seq) data to search for cell-type differences in HCC. To first identify HCC, adjacent non-tumor tissue, normal liver, we integrated single-cell level from healthy cohort ( n = 9 non-HCC samples) collected the Strasbourg University Hospital; an HCC 1 non-HCC, 14 HCC-tumor, Singapore General Hospital National University; another 3 HCC-tumor Dumont-UCLA Liver Cancer Center. then leveraged these decompose RNA-seq patients’ tumor 361) tissue 49) Genome Atlas (TCGA) multi-center cohort. For replication, decomposed 221 209 microarray samples Institute (LCI) by Zhongshan of Fudan University. Results discovered tumor-associated proliferative cell-type, Prol (80.4% cells), enriched cycle mitosis genes. In TCGA cohort, proportion significantly increased associates worse Independently our decomposition analysis, reciprocally show nuclei/cells over-express both tumor-elevated survival-decreasing genes obtained tissue. Our replication analysis LCI confirmed estimated significant marker shorter Finally, somatic mutations suppressor TP53 RB1 linked increase Conclusions By integrating cell, nucleus, expression multiple cohorts identified proliferating (Prol) tumors, associated decreased survival, mutations.

Language: Английский

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Spatial transcriptomics technology in cancer research

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 13, 2022

In recent years, spatial transcriptomics (ST) technologies have developed rapidly and been widely used in constructing tissue atlases characterizing spatiotemporal heterogeneity of cancers. Currently, ST has to profile multiple cancer types. Besides, is a benefit for identifying comprehensively understanding special areas such as tumor interface tertiary lymphoid structures (TLSs), which exhibit unique microenvironments (TMEs). Therefore, also shown great potential improve pathological diagnosis identify novel prognostic factors cancer. This review presents advances prospects applications on research based well the challenges.

Language: Английский

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Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 14, 2023

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cell signals, TAMs exhibit unparalleled adaptability, aligning with dynamic milieu. Their roles span from promoting growth and angiogenesis modulating metastasis. While substantial research has explored fundamentals of TAMs, comprehending their adaptive behavior, leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, complex orchestration cytokines chemokines determining functions. We highlight complexities TAM-targeted focusing on adaptability potential variability in therapeutic outcomes. Moreover, we discuss synergy integrating TAM-focused strategies established treatments, such as chemotherapy, immunotherapy. Emphasis is laid pioneering methods like reprogramming immunotherapy adoption single-cell technologies precision intervention. synthesis seeks shed light TAMs’ multifaceted cancer, pinpointing prospective pathways transformative enhancing modalities oncology.

Language: Английский

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Molecular and immune landscape of hepatocellular carcinoma to guide therapeutic decision-making

Hepatology, Journal Year: 2023, Volume and Issue: unknown

Published: June 10, 2023

Liver cancer, primarily HCC, exhibits highly heterogeneous histological and molecular aberrations across tumors within individual tumor nodules. Such intertumor intratumor heterogeneities may lead to diversity in the natural history of disease progression various clinical disparities patients. Recently developed multimodality, single-cell, spatial omics profiling technologies have enabled interrogation intertumor/intratumor heterogeneity cancer cells immune microenvironment. These features influence efficacy emerging therapies targeting novel pathways, some which had been deemed undruggable. Thus, comprehensive characterization at levels facilitate discovery biomarkers that enable personalized rational treatment decisions, optimize while minimizing risk adverse effects. companion will also refine HCC algorithms stages for cost-effective patient management by optimizing allocation limited medical resources. Despite this promise, complexity ever-expanding inventory therapeutic agents regimens made evaluation translation increasingly challenging. To address issue, trial designs proposed incorporated into recent studies. In review, we discuss latest findings landscape their potential utility as biomarkers, framework application predictive/prognostic ongoing biomarker-guided trials. new developments revolutionize care substantially impact still dismal mortality.

Language: Английский

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Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 6, 2023

A lack of relevant genetic models and cell lines hampers our understanding hepatoblastoma pathogenesis the development new therapies for this neoplasm. Here, we report an improved MYC-driven hepatoblastoma-like murine model that recapitulates pathological features embryonal type hepatoblastoma, with transcriptomics resembling high-risk gene signatures human disease. Single-cell RNA-sequencing spatial identify distinct subpopulations cells. After deriving from mouse model, map cancer dependency genes using CRISPR-Cas9 screening druggable targets shared (e.g., CDK7, CDK9, PRMT1, PRMT5). Our screen also reveals oncogenes tumor suppressor in engage multiple, signaling pathways. Chemotherapy is critical treatment. mapping doxorubicin response by identifies modifiers whose loss-of-function synergizes PRKDC) or antagonizes apoptosis genes) effect chemotherapy. The combination PRKDC inhibition doxorubicin-based chemotherapy greatly enhances therapeutic efficacy. These studies provide a set resources including disease suitable identifying validating potential hepatoblastoma.

Language: Английский

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