A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Lu, Yiming; Yang, Aiqing; Cheng, Quan; Pan, Yingwei; Zhang, Haoyun; Li, Yuanfeng; Gao, Chengming; Lu, Hao; Wang, Xueting; Cao, Pengbo; Chen, Hongxia; Lu, Shichun; Zhou, Gangqiao

doi:10.1038/s41467-022-32283-3

Cited by 194 publications

(188 citation statements)

References 63 publications

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“…Neutrophils are frequently dominant and are linked to immunological escape from tumors ( 18 ). Consequently, these findings imply that FCN2 may suppress the HCC tumor immune response by favorably regulating neutrophils ( 19 , 20 ), eosinophils ( 21 ), NK cells ( 22 – 24 ), Tcm ( 25 ), and DCs ( 26 – 28 ) and negatively regulating Th2 ( 29 – 31 ) in tumors.…”

Section: Discussionmentioning

confidence: 92%

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

Wang

Zeng²,

Jiang³

et al. 2022

Front. Oncol.

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ObjectiveThis study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.MethodsOncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.ResultsIn HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.ConclusionFCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

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Section: Discussionmentioning

confidence: 92%

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

Wang

Zeng²,

Jiang³

et al. 2022

Front. Oncol.

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“…We collected single-cell RNA transcriptome data from the GEO database (ID: GSE176078, GSE149614, and GSE160269) [ 62 , 63 , 64 ]. We analyzed the data above with the “Seurat V4” R package [ 65 ].…”

Section: Methodsmentioning

confidence: 99%

The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance

Xie

Zhang

Tian

et al. 2022

IJMS

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The forkhead box O (FOXO) transcription factors (TFs) family are frequently mutated, deleted, or amplified in various human cancers, making them attractive candidates for therapy. However, their roles in pan-cancer remain unclear. Here, we evaluated the expression, prognostic value, mutation, methylation, and clinical features of four FOXO family genes (FOXO1, FOXO3, FOXO4, and FOXO6) in 33 types of cancers based on the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. We used a single sample gene set enrichment analysis (ssGSEA) algorithm to establish a novel index called “FOXOs score”. Moreover, we investigated the association between the FOXOs score and tumor microenvironment (TME), the responses to multiple treatments, along with drug resistance. We found that the FOXO family genes participated in tumor progression and were related to the prognosis in various types of cancer. We calculated the FOXOs score and found that it was significantly correlated with multiple malignant pathways in pan-cancer, including Wnt/beta-catenin signaling, TGF-beta signaling, and hedgehog signaling. In addition, the FOXOs score was also associated with multiple immune-related characteristics. Furthermore, the FOXOs score was sensitive for predicting the efficacy of diverse treatments in multiple cancers, especially immunotherapy. In conclusion, FOXO family genes were vital in pan-cancer and were strongly correlated with the TME. A high FOXOs score indicated an excellent immune-activated TME and sensitivity to multiple treatments. Hence, the FOXOs score might potentially be used as a biomarker in patients with a tumor.

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“…TCGA pan cancer dataset was downloaded from https://gdc.cancer.gov/about-data/publications/pancanatlas. Single cell RNA-Seq datasets were downloaded from the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/) with the following accession numbers: GSE160269 (Esophageal Squamous cell carcinoma, ESCC) 25 , GSE144236 (cutaneous Squamous cell carcinoma, cSCC) 19 , GSE132465 (Colorectal Cancer, COREAD) 20 , GSE161529 (Brest Cancer, BRCA) 26 , GSE120575 (Melanoma, SKCM) 15 , GSE115978 (Melanoma, SKCM) 16 , GSE139829 (Uveal melanoma, UVM) 22 , GSE146026 (Ovarian cancer, OV) 21 , GSE131928 (Glioblastoma, GBM) 17 , GSE131907 (Lung adenocarcinoma, LUAD) 23 , GSE149614 (Hepatocellular carcinoma, HCC) 24 , GSE103322 (Head and neck Squamous cell carcinoma, HNSCC) 13 , GSE70630 (Low grade glioma – Oligodendroglioma, LGG) 12 and GSE89567 (Low grade glioma – Astrocytoma, LGG) 14 . For Pancreatic ductal adenocarcinoma (PAAD), Peng et al .…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the differential gene expression between normal and cancer cells, we performed the scRNA-Seq analysis of the datasets from ESCC 25 , cSCC 19 , COREAD 20 , BRCA 26 , LUAD 23 , HCC 24 and PDAC 18 . Data was normalized and scaled using the SCTransform function (regressing out the mitochondrial percentage), and Principal Component Analysis (PCA) was performed with the 3000 most variable genes.…”

Section: Methodsmentioning

confidence: 99%

The transcriptional landscape of glycosylation-related genes in cancer

Rodríguez

Lindijer

Vliet

et al. 2022

Preprint

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Changes in glycosylation patterns have been associated with malignant transformation and clinical outcome in several types of cancer, although no comprehensive analysis has been performed in a pan-cancer setting. Here, we performed an extensive transcriptomic analysis of glycosylation related genes (such as enzymes involved in synthesis and degradation of glycoconjugates, transporters, mucins and galectins), using publicly available bulk and single cell transcriptomic data sets from tumor samples and cancer cell lines. We identified genes and pathways associated with different tumor types, which may represent novel diagnostic biomarkers as α2-3 sialylation for Melanoma, MUC21 for Lung adenocarcinoma and Galectin-7 for Squamous cell carcinomas (SCC). Accordingly, serum levels of Galectin-7 in patients with lung cancer were elevated in SCC respect to adenocarcinomas, supporting its biomarker potential. Moreover, we characterized the contribution of different cell types to the overall glycosylation profiles observed by performing the integration and analysis of 14 single cell RNA-seq datasets. This led us to identify that cancer cells are responsible for the specific tumor glyco-codes identified in bulk transcriptomics, while stromal and immune cells contribute in a conserved manner across various malignancies. Furthermore, our results suggest that the glycosylation-related genes and pathways expressed by cancer cells are influenced by the cell of origin and the oncogenic pathways that led to malignant transformation. Lastly, we described the association of different glycosylation-related genes and pathways with the clinical outcome of patients. Interestingly, while the expression of genes associated to some pathways (as proteoglycan biosynthesis) are consistently associated with a more aggressive disease, the correlation of others pathways with the survival of patients depends on the particular tumor type. Remarkably, the expression of genes associated with the synthesis of CMP-sialic acid was correlated with lower survival of patients in Uveal Melanoma and PDAC, while the opposite was observed for colorectal cancer. The extensive transcriptomic analysis of glycosylation pathways in cancer that we report here can serve as a resource for future research aimed to unravel the glyco-code in cancer related to clinical outcome or biomarker development.

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A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Cited by 194 publications

References 63 publications

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance

The transcriptional landscape of glycosylation-related genes in cancer

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