Single-Cell RNA-Seq Analysis Reveals Microenvironmental Infiltration of Plasma Cells and Hepatocytic Prognostic Markers in HCC With Cirrhosis

Zhang, Siwen; Liu, Zhenhao; Wu, Dan; Chen, Lanming; Xie, Lu

doi:10.3389/fonc.2020.596318

Cited by 52 publications

(59 citation statements)

References 45 publications

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“…In our study, infiltration of memory B cells, activated memory CD4 + T cells, T follicular helper (Tfh) cells, and naive CD4 + T cells was upregulated while infiltration of naive B cells was downregulated in high-risk patients. It was reported that there was more B cells infiltration in HCC patients than in patients with cirrhosis and healthy people ( Zhang et al, 2020 ). Upregulation of plasma cells and lower expression of naive B cells correlated with poorer prognosis ( Zhang Z. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC

Zhao

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Background: Hepatocellular carcinoma (HCC) is the world’s second most deadly cancer, and metabolic reprogramming is its distinguishing feature. Among metabolite profiling, variation in amino acid metabolism supports tumor proliferation and metastasis to the most extent, yet a systematic study on the role of amino acid metabolism-related genes in HCC is still lacking. An effective amino acid metabolism-related prediction signature is urgently needed to assess the prognosis of HCC patients for individualized treatment.Materials and Methods: RNA-seq data of HCC from the TCGA-LIHC and GSE14520 (GPL3921) datasets were defined as the training set and validation set, respectively. Amino acid metabolic genes were extracted from the Molecular Signature Database. Univariate Cox and LASSO regression analyses were performed to build a predictive risk signature. K-M curves, ROC curves, and univariate and multivariate Cox regression were conducted to evaluate the predictive value of this risk signature. Functional enrichment was analyzed by GSEA and CIBERSORTx software.Results: A nine-gene amino acid metabolism-related risk signature including B3GAT3, B4GALT2, CYB5R3, GNPDA1, GOT2, HEXB, HMGCS2, PLOD2, and SEPHS1 was constructed to predict the overall survival (OS) of HCC patients. Patients were separated into high-risk and low-risk groups based on risk scores and low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for HCC. ROC curves showed that this risk signature can effectively predict the 1-, 2-, 3- and 5-year survival times of patients with HCC. Additionally, prognostic nomograms were established based on the training set and validation set. These genes were closely correlated with the immune regulation.Conclusion: Our study identified a nine-gene amino acid metabolism-related risk signature and built predictive nomograms for OS in HCC. These findings will help us to personalize the treatment of liver cancer patients.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC

Zhao

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Particularly worrying are the elevated levels of CCL20, which is a pro-angiogenic factor that promotes HCC hypervascularization (81) and might be behind the increased probability of developing HCC following SVR (82)(83)(84). High gene expression levels of CXCL3, CXCL8, and IL1A also correlate with HCV-associated liver inflammation, cirrhosis, and HCC (85)(86)(87)(88)(89). Overexpression of TNFSF15 increases inflammation and both liver and intestinal fibrosis, promoting chronic immunological diseases (90,91).…”

Section: Discussionmentioning

confidence: 99%

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients

et al. 2021

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Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways (“cytokine-cytokine receptor interaction”, “viral protein interaction with cytokine and cytokine receptor”, “chemokine signaling pathway”, and “hepatitis C”). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.

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“…Five subclusters of cells were identified from the GCTB lesion: C1_CD8 + T cells, C2_T cells, C3_T cells, C4_NK cells and C5_ CD8 + T cells ( Figures 5A, B ). C1_CD8 + T cells, and C2_CD8 + T cells shared specific T-cell markers genes, such as CD3D, CD3E, CD3G, CD8A, and CD8B ( 19 , 45 ). C2_T cells and C3_T cells expressed CD3D, CD3E, and CD3G.…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

Feng

Jiang

et al. 2021

Front. Oncol.

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Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

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Single-Cell RNA-Seq Analysis Reveals Microenvironmental Infiltration of Plasma Cells and Hepatocytic Prognostic Markers in HCC With Cirrhosis

Cited by 52 publications

References 45 publications

Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC

Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

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