Comprehensive analysis of spatial architecture in primary liver cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu R
PROVIDER: S-EPMC8683021 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.
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Project description:Using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) from a high-resolution perspective.
2024-01-26 | PXD044778 | Pride
Project description:Metastasis is one of the leading causes of cancer-related deaths. A comprehensive comparison of the differences between primary and metastatic cancers within the same organ can aid in understanding the growth mechanisms of cancer cells at metastatic sites, thereby helping to develop more effective targeted treatment strategies. Primary liver cancer is one of the most common types of cancer, and the liver is also one of the main metastatic sites. In this paper, we utilize single-cell RNA-Seq data to compare primary liver cancer and colorectal liver metastases from multiple perspectives, including cell types and proportions, activity of various cell types, cell-cell communication, mRNA expression differences within the same types of cells, key factors associated with cell proliferation, etc. Our analysis results show the following: (i) Compared to primary tissue, metastatic tissue contains more cytotoxic T cells and exhausted T cells, and it retains some specific characteristics of the primary site. (ii) Cells of the same type exhibit functional differences between primary and metastatic cancers, with metastatic cancer cells showing lower metabolism levels and immune cells exhibiting stronger immune activity. (iii) Interactions between monocytes and hepato-associated cells are strong in primary cancer, while depleted T cells frequently communicate with hepatocytes in metastatic cancer. (iv) Proliferation-related genes in primary and metastatic cancers are mainly involved in cell energy supply and basic metabolism activity, respectively.
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Project description:Multiple primary lung cancers (MPLC) pose diagnostic and therapeutic challenges in the clinic. Here, we orchestrated the cellular atlas and spatial architecture of MPLC based on spatial transcriptomics.
2022-04-23 | GSE200916 | GEO
Project description:The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially resolved single-cell transcriptomics revealed that about half of hepatocyte genes are differentially expressed across the lobule, yet technical limitations impeded reconstructing similar global spatial maps of other hepatocyte features. Here, we show how zonated surface markers can be used to sort hepatocytes from defined lobule zones with high spatial resolution. We apply transcriptomics, miRNA array measurements and mass spectrometry proteomics to reconstruct spatial atlases of multiple zonated features. We demonstrate that protein zonation largely overlaps with mRNA zonation, with the periportal HNF4? as an exception. We identify zonation of miRNAs such as miR-122, and inverse zonation of miRNAs and their hepatocyte target genes, highlighting potential regulation of protein levels through zonated mRNA degradation. Among the targets we find the pericentral Wnt receptors Fzd7 and Fzd8 and the periportal Wnt inhibitors Tcf7l1 and Ctnnbip1. Our approach facilitates reconstructing spatial atlases of multiple cellular features in the liver and other structured tissues.
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Project description:BackgroundLiver cancer is one of the most common cancers in the world, with unique regional variations in disability-adjusted life years (DALY) rate, nearly 50% of liver cancer cases occur in China. Therefore, understanding the epidemiological characteristics of liver cancer is of utmost importance. In this study, to analyze the spatial distribution characteristics and clustering of the DALY rate of liver cancer in 1990 and 2017 in China based on provincial administrative divisions, and to explore its possible influencing factor.MethodsThe DALY rate data of liver cancer at the provincial level in China were collected, the global autocorrelation of the DALY rate was analyzed by Moran's I, the local autocorrelation of the DALY rate was analyzed by Getis-Ord-Gi*, and the influencing factors related to the DALY rate were analyzed by the least squares regression model.ResultsThe DALY rate of liver cancer in China generally showed an increasing trend. The DALY rate increased in 22 provinces and decreased in nine provinces. In 2017, the distribution of DALY rate in all provinces showed heterogeneity, with the highest DALY rate in Guangxi (1,363.37/100,000) and the lowest in Beijing (315.78/100,000). In 2017, the low and low clustering were mainly concentrated in Inner Mongolia, Ningxia, Shanxi, Hebei, and Tianjin. The low and high clustering in Yunnan, Guizhou, and Guangdong, were surrounded by the high clustering in neighboring provinces, high and high concentration is mainly concentrated in Hunan and neighboring provinces. The results of the least square regression model showed that the per capita years of education, hepatitis B incidence and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer (P<0.05).ConclusionsThe DALY rate of liver cancer in China showed an overall increasing trend. In 2017, the DALY rate of liver cancer in China had a spatial aggregation in the whole country, and the per capita years of education, the incidence of hepatitis B and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer in space.
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Project description:Spatial transcriptomics based characterization of spatial architecture in human multiple primary lung cancer
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Project description:The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type (WT) and Tet2-/- fetal livers, by multiplexed error robust fluorescence in situ hybridization. We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor signaling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are in direct contact with endothelial cells (ECs) in both WT and Tet2-/- fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs, arterial ECs and sinusoidal ECs, and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.
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Project description:Primary liver cancer (PLC), consisting mainly of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is one of the major causes of cancer-related mortality worldwide. The curative therapy for PLC is surgical resection and liver transplantation, but most PLCs are inoperable at diagnosis. Even after surgery, there is a high rate of tumor recurrence. There is an unmet clinical need to discover more effective treatment options for advanced PLCs. Pre-clinical mouse models in PLC research have played a critical role in identifying key oncogenic drivers and signaling pathways in hepatocarcinogenesis. Furthermore, recent advances in single-cell RNA sequencing (scRNA-seq) have provided an unprecedented degree of resolution in such characterization. In this review, we will summarize the recent studies that utilized pre-clinical mouse models with the combination of scRNA-seq to provide an understanding of different aspects of PLC. We will focus particularly on the potentially actionable targets regarding the cellular and molecular components. We anticipate that the findings in mouse models could complement those in patients. With more defined etiological background, mouse models may provide valuable insights.
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Project description:The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV) integration sites are frequently detected within inactive chromatin regions in cancer cells, as a consequence of negative selection for integrations in active chromatin regions. Ultra-high structural instability and preserved unmethylation of integrated HBV genomes are observed. We conclude that both precancerous and somatic epigenetic features contribute to the cancer genome architecture.
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