Comprehensive analysis of spatial architecture in primary liver cancer

Wu, Rui; Guo, Wu; Qiu, Xinyao; Wang, Shicheng; Sui, Chengjun; Lian, Qiuyu; Wu, Jianmin; Shan, Yiran; Zhao, Yang; Yang, Shuai; Wu, Tong; Wang, Kaiting; Zhu, Yanjing; Wang, Shan; Liu, Changyi; Zhang, Yangqianwen; Zheng, Bo; Li, Zhixuan; Zhang, Yani; Shen, Siyun; Zhao, Yan; Wang, Wenwen; Bao, Jinxia; Hu, Ji; Wu, Xuan; Jiang, Xiaoqing; Wang, Hongyang; Gu, Jin; Chen, Lei

doi:10.1126/sciadv.abg3750

Cited by 196 publications

(192 citation statements)

References 67 publications

(104 reference statements)

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“…Given the limits of tissue samples, we further performed a secondary data analysis on a previous study of ST sequencing on primary liver cancers, which also presented spatial transcriptome map of three major liver cancer subtypes 23 . In order to better match the spatial location of our tissue samples with higher spatial continuity that includes the carcinoma, fiber cord sector to para-carcinoma sector, we chose the leading-edge section of 4 HCC samples from their ST data and annotated them as HCC1, HCC2, HCC3, and HCC4 ( Figure S2 A).…”

Section: Resultsmentioning

confidence: 99%

“…ST was first applied in the mouse brain and human breast cancer to verify the feasibility of spatial visualization and quantitative analysis of gene expression 15 ; it was then used to explore the spatial discrepancy of gene expression in dynamic disease processes, such as amyotrophic lateral sclerosis 16 and Alzheimer's disease 17 , as well as in normal tissue development processes 18 . Moreover, ST is conducive to resolving spatial heterogeneity and spatial gene expression patterns in various tumors, such as prostate cancer 19 , melanoma 20 and pancreatic ductal adenocarcinoma 21 , and primary liver cancer 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

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Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment

Wang¹,

Yuan²,

Jiang³

et al. 2022

Theranostics

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Rationale: Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant disease with the complex immune microenvironment, which ultimately influence clinic outcomes of patients. However, the spatial expression patterns of diverse immune cells among tumor microenvironment remain to be further deciphered. Methods: Spatial transcriptomics sequencing (ST) was implemented on two portions of HCC specimens. Differentially expressed genes, cell cycle phases, epithelial-mesenchymal features, pseudo-time and immune infiltration analysis were applied to demonstrate the intratumor heterogeneity and define the specific immune-related regions, and the results were further validated by a second analysis on another ST study. In vitro and in vivo experiments were conducted to confirm the functional mechanisms of key molecules such as CCL15, CCL19 and CCL21. Clinical tissue samples were used to assess their potential prognostic and therapeutic values. Results: Totally, 7553 spots were categorized into 15 subsets by hierarchical clustering, and malignant subsets with intratumor heterogeneity phenotypes were identified. Spatial heterogeneity from distinct sectors highlights specific chemokines: CCL15 is remarkable in the core region of the carcinoma sector and facilitates the immunosuppressive microenvironment by recruiting and polarizing M2-like macrophages in vitro and in vivo ; High expression of CCL15 and CD163 respectively predicts poor prognosis of HCC patients, and the combined application of them has better predictive value. CCL19 and CCL21, sharing similar spatial expression patterns, are highly-correlated and prominent in the immune infiltration enrichment and recruit CD3 + T cells and CD20 + B cells to inhibit the growth of HCC, indicating a good prognosis of HCC patients. Conclusions: Taken together, our studies preliminarily reveal intratumor heterogeneity of HCC based on ST techniques and unravel the previously unexplored spatial expression patterns in the immune microenvironment. We also highlight the clinical significance and spatial discrepancy of key molecules, providing novel insight for further developing therapeutic strategies in HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment

Wang¹,

Yuan²,

Jiang³

et al. 2022

Theranostics

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“…High-resolution spatial transcriptomes of PLCs were constructed by scRNA-seq to reveal the extensive global and local intratumor heterogeneities of tumors and TMEs ( 115 ). It was reported to be the first study to analyze the genome-wide TME characteristics from normal to leading-edge to tumor regions, identifying the vital role of complete fibrous capsule for both TME architecture and intratumor heterogeneity.…”

Section: Applications Of Single-cell Sequencing In Liver Cancermentioning

confidence: 99%

“…Wu et al. progressively compared the spatial TME characteristics from nontumor to leading-edge to tumor regions, demonstrating that the tumor capsule potentially affected intratumor spatial cluster continuity, transcriptome diversity, and immune cell infiltration ( 115 ). Their results revealed that the integrity of the capsule was closely related to the distribution of their surrounding stromal and immune cells but had few effects on the activities of hallmark pathways in neither normal nor tumor regions.…”

Section: Applications Of Single-cell Sequencing In Liver Cancermentioning

confidence: 99%

Single-Cell Sequencing and Its Applications in Liver Cancer

Tian

2022

Front. Oncol.

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As one of the most lethal cancers, primary liver cancer (PLC) has high tumor heterogeneity, including the heterogeneity between cancer cells. Traditional methods which have been used to identify tumor heterogeneity for a long time are based on large mixed cell samples, and the research results usually show average level of the cell population, ignoring the heterogeneity between cancer cells. In recent years, single-cell sequencing has been increasingly applied to the studies of PLCs. It can detect the heterogeneity between cancer cells, distinguish each cell subgroup in the tumor microenvironment (TME), and also reveal the clonal characteristics of cancer cells, contributing to understand the evolution of tumor. Here, we introduce the process of single-cell sequencing, review the applications of single-cell sequencing in the heterogeneity of cancer cells, TMEs, oncogenesis, and metastatic mechanisms of liver cancer, and discuss some of the current challenges in the field.

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“…However, more effort is necessary to identify the specific mechanism. Additionally, recent excellent work- based spatial transcriptomics technology has revealed intense contact between LCSCs and vascular infiltration, which also seems to suggest a robust relationship between the two components [ 86 ]. Together, more evidence from several novel technologies, such as spatial and single-cell transcriptomics, might provide more awareness and inspiration about the topic.…”

Section: The Tme and Liver Cancer Stemness Maintenancementioning

confidence: 99%

Mechanism of cancer stemness maintenance in human liver cancer

Liang

Yang²,

Huang³

et al. 2022

Cell Death Dis

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Primary liver cancer mainly includes the following four types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA). Recent studies have indicated that there are differences in cancer stem cell (CSC) properties among different types of liver cancer. Liver cancer stem cells (LCSCs), also called liver tumor-initiating cells, have been viewed as drivers of tumor initiation and metastasis. Many mechanisms and factors, such as mitophagy, mitochondrial dynamics, epigenetic modifications, the tumor microenvironment, and tumor plasticity, are involved in the regulation of cancer stemness in liver cancer. In this review, we analyze cancer stemness in different liver cancer types. Moreover, we further evaluate the mechanism of cancer stemness maintenance of LCSCs and discuss promising treatments for eradicating LCSCs.

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Comprehensive analysis of spatial architecture in primary liver cancer

Abstract: Spatial transcriptome technique was applied to decipher the spatial architecture and TME characteristics of liver cancers.

Cited by 196 publications

References 67 publications

Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment

Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment

Single-Cell Sequencing and Its Applications in Liver Cancer

Mechanism of cancer stemness maintenance in human liver cancer

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