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Single-cell dissection of the multicellular ecosystem and molecular feature sunderlying microvascular invasion in hepatocellular carcinoma

ABSTRACT: Single-cell dissection of the multicellular ecosystem and molecular feature sunderlying microvascular invasion in hepatocellular carcinoma

PROVIDER: PRJNA1015233 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26035075_1.fastq.gz	Fastqsanger.gz
	SRR26035075_2.fastq.gz	Fastqsanger.gz
	SRR26035076_1.fastq.gz	Fastqsanger.gz
	SRR26035076_2.fastq.gz	Fastqsanger.gz
	SRR26035077.fastq.gz	Fastqsanger.gz

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Single-cell dissection of the multicellular ecosystem and molecular feature sunderlying microvascular invasion in hepatocellular carcinoma

Project description:Microvascular invasion (MVI) is a significant pathological feature of hepatocellular carcinoma (HCC) associated with poor outcomes, early recurrence, and intrahepatic metastasis in post-surgical resection and transplant patients. However, the tumor microenvironment (TME) and transcriptional programs underlying MVI remain poorly understood. In this study, we conducted single-cell RNA sequencing of 46,789 individual cells from 10 samples of MVI+ (MVI present) and MVI- (MVI absent) HCC patients, providing a comprehensive single-cell atlas of MVI. Single-cell dissection of the multicellular ecosystem revealed the emergence or expansion of cycling T cells, LAMP3+ dendritic cells, TREM2+ macrophages, myofibroblasts, and tumor-promoting arterial i endothelial cells within the MVI+ TME. MVI+ malignant cells are characterized by high proliferation rates and the ability to evade immune detection through the upregulation of non-classical MHC class I molecules. In contrast, MVI-malignant cells exhibit an inflammatory milieu. Furthermore, we identified the CCL16/CCR1 interaction between TREM2+ macrophages and malignant cells as a contributing factor in MVI formation and tumor progression. Notably, we identified a unique multicellular module that plays the dominant role in shaping the immunosuppressive microenvironment of MVI and correlates with poor prognosis. In summary, these findings enhance our understanding of the underlying cellular and molecular mechanisms driving MVI and provide valuable insights for improving clinical diagnosis and developing more effective treatment strategies.

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Single-cell RNA sequencing reveals intratumoral heterogeneity and multicellular community in primary hepatocellular carcinoma underlying microvascular invasion.

Project description:BackgroundMicrovascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI).MethodsWe performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues.ResultsWe identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis.ConclusionsWe provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

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Noninvasive urinary protein signatures combined clinical information associated with Microvascular Invasion Risk in patients with HCC

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