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Editor-in-Chief | Enzyma's primary liver cancer is the fourth most deadly malignant tumor in the world [1]
.
The highly complex tumor and tumor microenvironment heterogeneity are the key factors that cause the progression and treatment failure of primary liver cancer [2-3].
Therefore, systematic evaluation of tumor heterogeneity is effective for understanding the biological mechanism of tumor occurrence and development and research and development.
The treatment method is crucial
.
The heterogeneity of primary liver cancer includes two dimensions of time and space [4].
The single-cell omics technology that has gradually matured in recent years has greatly expanded the understanding of the heterogeneity of primary liver cancer, but single-cell omics detection The spatial location information of the cells is lost, and the spatial distribution characteristics of different cell types or subgroups in the tumor microenvironment cannot be restored
.
On December 17, 2021, the team of Academician Hongyang Wang/Lei Chen of the National Liver Cancer Science Center of Naval Military Medical University and the team of Associate Professor Gu Jin of Tsinghua University jointly published a research paper on Comprehensive analysis of spatial architecture in primary liver cancer in Science Advances
.
This paper applies the 10X Genomics high-resolution spatial transcriptomics technology (Spatial Transcriptomics, ST) to the study of the boundary zone and intratumoral spatial heterogeneity of primary liver cancer, and is the first to map the high-resolution space of primary liver cancer in the world Molecular map
.
The papers published atlas include three subtypes of hepatocellular carcinoma (5 cases), mixed liver cancer (1 case), intrahepatic cholangiocarcinoma (1 case), paracarcinoma, cancer-pericarcinoma boundary, cancer primary tumor, and portal vein cancer Shuan has a total of 21 samples and 84823 effective spatial points
.
The thesis systematically analyzed the spatial distribution characteristics of stroma and immune cells in the tumor microenvironment (especially the tumor-paracancerous interface), the functional differences and interactions between tumor cell subgroups, the diversity of the tumor stem microenvironment, and the tertiary lymphatic structure (Tertiary Lymphoid Structure, TLS) spatial distribution and molecular characteristics
.
These findings provide new insights into the spatial heterogeneity and biological characteristics of liver cancer tumor cells and microenvironmental cells, and also preliminarily demonstrate the great significance of high-resolution spatial maps for the individualized treatment and drug discovery of liver cancer
.
Researchers performed spatial transcriptomics sequencing on samples from 21 different locations in 7 patients with PLC, and obtained sequencing information of 84823 effective spatial sequencing sites (spots), combined with whole-exome sequencing of matched tissue samples (Whole-exome sequencing).
The results of sequencing, WES) showed that: 1.
The internal subgroups of primary liver cancer have two spatial distribution patterns: regional distribution and staggered distribution; 2.
The relationship between the tumor fiber envelope in the PLC border area and the immune microenvironment in this area Heterogeneity correlation: when there is a tumor envelope in the border area, the distribution of immune cells in the normal liver tissue outside the envelope is more than that in the inner tumor tissue; when there is no tumor envelope, the degree of immune cell infiltration in the tumor border area is overall Enhanced and exhaustive T cells increase, and the distribution of immune cells on both sides of the tumor border is more disordered; 3.
Different subgroups within the tumor have different dominant gene expression, cell function, prognosis, and cloning sources, and the subgroups within the tumor are not independent A wide range of ligand-receptor interactions will occur in the range of contact with each other (100μm wide junction area); 4.
The enrichment of PROM1+ and CD47+ CSC is positively correlated with HCC tumor invasion and migration; 5.
A new product has been developed.
TLS-50, a gene set used to identify tertiary lymphatic structure, and found in the TCGA (The Cancer Genome Atlas) database that a high score of TLS-50 is associated with a better prognosis of primary liver cancer
.
At the same time, the expression of some characteristic genes of TLS is affected by the distance from the tumor tissue, and the expression of some characteristic genes inside TLS also changes gradually from the center to the periphery
.
Finally, the researchers also performed a 2D panoramic spatial heterogeneity analysis on a case of early liver cancer, and used four chips to draw a global transcriptome map of the entire tumor section
.
The analysis found that the spatial pattern of regional distribution and staggered distribution has coexisted in early liver cancer, and the spatial distribution of early liver cancer presents an asymmetric (neither axisymmetric or non-centrosymmetric) pattern
.
After subdividing the center of the tumor with 16 radiation directions and 18 concentric gradients, the researchers also found that tumor cell function has completely different gradient changes in different radiation directions from the center to the surroundings
.
This part of the results further shows that the internal spatial heterogeneity of liver tumors is highly complex, and the relationship between the spatial heterogeneity of its microenvironment and the effectiveness of immune or targeted therapy deserves further study
.
Academician Wang Hongyang and Researcher Chen Lei of the National Liver Cancer Science Center of Naval Military Medical University, Associate Professor Gu Jin from the Department of Automation of Tsinghua University are the co-corresponding authors of the paper, Wu Rui, a doctoral candidate in the Eastern Hepatobiliary Surgery Hospital, Guo Wenbo, a doctoral candidate in the Department of Automation of Tsinghua University, and Affiliated Tumor Hospital of Fudan University Postdoctoral fellow Qiu Xinyao is the co-first author of the paper
.
Original link: https://doi.
org/10.
1126/sciadv.
abg3750 Platemaker: Eleven References 1.
Villanueva A.
Hepatocellular Carcinoma [J].
N Engl J Med, 2019, 380(15): 1450-62.
2.
Li L, Wang H.
Heterogeneity of liver cancer and personalized therapy [J].
Cancer Lett, 2016, 379(2): 191-7.
3.
Losic B, Craig AJ, Villacorta-Martin C, et al.
Intratumoral heterogeneity and clonal evolution in liver cancer [J].
Nat Commun, 2020, 11(1): 291.
4.
Dagogo-Jack I, Shaw A T.
Tumour heterogeneity and resistance to cancer therapies [J].
Nature reviews Clinical oncology, 2018, 15(2) : 81-94.
Reprinting instructions [Non-original articles] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights, and offenders must be investigated
.
.
The highly complex tumor and tumor microenvironment heterogeneity are the key factors that cause the progression and treatment failure of primary liver cancer [2-3].
Therefore, systematic evaluation of tumor heterogeneity is effective for understanding the biological mechanism of tumor occurrence and development and research and development.
The treatment method is crucial
.
The heterogeneity of primary liver cancer includes two dimensions of time and space [4].
The single-cell omics technology that has gradually matured in recent years has greatly expanded the understanding of the heterogeneity of primary liver cancer, but single-cell omics detection The spatial location information of the cells is lost, and the spatial distribution characteristics of different cell types or subgroups in the tumor microenvironment cannot be restored
.
On December 17, 2021, the team of Academician Hongyang Wang/Lei Chen of the National Liver Cancer Science Center of Naval Military Medical University and the team of Associate Professor Gu Jin of Tsinghua University jointly published a research paper on Comprehensive analysis of spatial architecture in primary liver cancer in Science Advances
.
This paper applies the 10X Genomics high-resolution spatial transcriptomics technology (Spatial Transcriptomics, ST) to the study of the boundary zone and intratumoral spatial heterogeneity of primary liver cancer, and is the first to map the high-resolution space of primary liver cancer in the world Molecular map
.
The papers published atlas include three subtypes of hepatocellular carcinoma (5 cases), mixed liver cancer (1 case), intrahepatic cholangiocarcinoma (1 case), paracarcinoma, cancer-pericarcinoma boundary, cancer primary tumor, and portal vein cancer Shuan has a total of 21 samples and 84823 effective spatial points
.
The thesis systematically analyzed the spatial distribution characteristics of stroma and immune cells in the tumor microenvironment (especially the tumor-paracancerous interface), the functional differences and interactions between tumor cell subgroups, the diversity of the tumor stem microenvironment, and the tertiary lymphatic structure (Tertiary Lymphoid Structure, TLS) spatial distribution and molecular characteristics
.
These findings provide new insights into the spatial heterogeneity and biological characteristics of liver cancer tumor cells and microenvironmental cells, and also preliminarily demonstrate the great significance of high-resolution spatial maps for the individualized treatment and drug discovery of liver cancer
.
Researchers performed spatial transcriptomics sequencing on samples from 21 different locations in 7 patients with PLC, and obtained sequencing information of 84823 effective spatial sequencing sites (spots), combined with whole-exome sequencing of matched tissue samples (Whole-exome sequencing).
The results of sequencing, WES) showed that: 1.
The internal subgroups of primary liver cancer have two spatial distribution patterns: regional distribution and staggered distribution; 2.
The relationship between the tumor fiber envelope in the PLC border area and the immune microenvironment in this area Heterogeneity correlation: when there is a tumor envelope in the border area, the distribution of immune cells in the normal liver tissue outside the envelope is more than that in the inner tumor tissue; when there is no tumor envelope, the degree of immune cell infiltration in the tumor border area is overall Enhanced and exhaustive T cells increase, and the distribution of immune cells on both sides of the tumor border is more disordered; 3.
Different subgroups within the tumor have different dominant gene expression, cell function, prognosis, and cloning sources, and the subgroups within the tumor are not independent A wide range of ligand-receptor interactions will occur in the range of contact with each other (100μm wide junction area); 4.
The enrichment of PROM1+ and CD47+ CSC is positively correlated with HCC tumor invasion and migration; 5.
A new product has been developed.
TLS-50, a gene set used to identify tertiary lymphatic structure, and found in the TCGA (The Cancer Genome Atlas) database that a high score of TLS-50 is associated with a better prognosis of primary liver cancer
.
At the same time, the expression of some characteristic genes of TLS is affected by the distance from the tumor tissue, and the expression of some characteristic genes inside TLS also changes gradually from the center to the periphery
.
Finally, the researchers also performed a 2D panoramic spatial heterogeneity analysis on a case of early liver cancer, and used four chips to draw a global transcriptome map of the entire tumor section
.
The analysis found that the spatial pattern of regional distribution and staggered distribution has coexisted in early liver cancer, and the spatial distribution of early liver cancer presents an asymmetric (neither axisymmetric or non-centrosymmetric) pattern
.
After subdividing the center of the tumor with 16 radiation directions and 18 concentric gradients, the researchers also found that tumor cell function has completely different gradient changes in different radiation directions from the center to the surroundings
.
This part of the results further shows that the internal spatial heterogeneity of liver tumors is highly complex, and the relationship between the spatial heterogeneity of its microenvironment and the effectiveness of immune or targeted therapy deserves further study
.
Academician Wang Hongyang and Researcher Chen Lei of the National Liver Cancer Science Center of Naval Military Medical University, Associate Professor Gu Jin from the Department of Automation of Tsinghua University are the co-corresponding authors of the paper, Wu Rui, a doctoral candidate in the Eastern Hepatobiliary Surgery Hospital, Guo Wenbo, a doctoral candidate in the Department of Automation of Tsinghua University, and Affiliated Tumor Hospital of Fudan University Postdoctoral fellow Qiu Xinyao is the co-first author of the paper
.
Original link: https://doi.
org/10.
1126/sciadv.
abg3750 Platemaker: Eleven References 1.
Villanueva A.
Hepatocellular Carcinoma [J].
N Engl J Med, 2019, 380(15): 1450-62.
2.
Li L, Wang H.
Heterogeneity of liver cancer and personalized therapy [J].
Cancer Lett, 2016, 379(2): 191-7.
3.
Losic B, Craig AJ, Villacorta-Martin C, et al.
Intratumoral heterogeneity and clonal evolution in liver cancer [J].
Nat Commun, 2020, 11(1): 291.
4.
Dagogo-Jack I, Shaw A T.
Tumour heterogeneity and resistance to cancer therapies [J].
Nature reviews Clinical oncology, 2018, 15(2) : 81-94.
Reprinting instructions [Non-original articles] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights, and offenders must be investigated
.
