TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

Sun, Dongqing; Wang, Jin; Han, Ya; Dong, Xin; Ge, Jun; Zheng, Rongbin; Shi, Xiaoying; Wang, Binbin; Li, Ziyi; Ren, Pengfei; Sun, Lishan; Yan, Yao; Zhang, Peng; Zhang, Fan; Li, Taiwen; Wang, Chenfei

doi:10.1093/nar/gkaa1020

Cited by 664 publications

(546 citation statements)

References 41 publications

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“…The 7307 CD8+ T cell type-specific genes in UM (Supplementary Table 1) were obtained from the Tumor Immune Single-Cell Hub (TISCH) website 2 , which is a single-cell RNA-seq database and aims to characterize tumor microenvironment at single-cell resolution (Sun et al, 2021). Next, the cutoff criterion of | log2 FC| ≥ 0.5 and adjusted p values < 0.05 were applied to screen the different expressed genes (DEGs) in CD8+ T cells.…”

Section: Identification Of Cd8+ T Cell-associated Immune-related Genes In Uveal Melanomamentioning

confidence: 99%

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma

Sun

Yuan

et al. 2021

Front. Cell Dev. Biol.

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BackgroundCD8+ T cells work as a key effector of adaptive immunity and are closely associated with immune response for killing tumor cells. It is crucial to understand the role of tumor-infiltrating CD8+ T cells in uveal melanoma (UM) to predict the prognosis and response to immunotherapy.Materials and MethodsSingle-cell transcriptomes of UM with immune-related genes were combined to screen the CD8+ T-cell-associated immune-related genes (CDIRGs) for subsequent analysis. Next, a prognostic gene signature referred to tumor-infiltrating CD8+ T cells was constructed and validated in several UM bulk RNA sequencing datasets. The risk score of UM patients was calculated and classified into high- or low-risk subgroup. The prognostic value of risk score was estimated by using multivariate Cox analysis and Kaplan–Meier survival analysis. Moreover, the potential ability of gene signature for predicting immunotherapy response was further explored.ResultsIn total, 202 CDIRGs were screened out from the single-cell RNA sequencing of GSE139829. Next, a gene signature containing three CDIRGs (IFNGR1, ANXA6, and TANK) was identified, which was considered as an independent prognostic indicator to robustly predict overall survival (OS) and metastasis-free survival (MFS) of UM. In addition, the UM patients were classified into high- and low-risk subgroups with different clinical characteristics, distinct CD8+ T-cell immune infiltration, and immunotherapy response. Gene set enrichment analysis (GSEA) showed that immune pathways such as allograft rejection, inflammatory response, interferon alpha and gamma response, and antigen processing and presentation were all positively activated in low-risk phenotype.ConclusionOur work gives an inspiration to explain the limited response for the current immune checkpoint inhibitors to UM. Besides, we constructed a novel gene signature to predict prognosis and immunotherapy responses, which may be regarded as a promising therapeutic target.

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Section: Identification Of Cd8+ T Cell-associated Immune-related Genes In Uveal Melanomamentioning

confidence: 99%

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma

Sun

Yuan

et al. 2021

Front. Cell Dev. Biol.

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“…The scRNA sequencing datasets were collected from the TISCH database (http://tisch.comp-genomics.org/home/) (21), which provided detailed cell-type annotation at the single-cell level, enabling the exploration of TME across different cancer types.…”

Section: Scrna Sequencing Datasets Acquisitionmentioning

confidence: 99%

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

Miao

Jiang

et al. 2021

Front. Oncol.

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The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.

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“…TISCH 23 ( http://tisch.comp-genomics.org ) is a scRNA-seq database, which aims to characterize the tumor microenvironment at single-cell resolution and adopt a uniform analysis pipeline to perform quality control, clustering, and cell-type annotation for each collected dataset. GSE103322 is a primary HNSCC dataset of TISCH; it contains data from 5902 single cells from 18 patients.…”

Section: Methodsmentioning

confidence: 99%

High SQLE Expression and Gene Amplification Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma

Liu¹,

Fang²,

Liu³

2021

CMAR

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Objective Squalene epoxidase (SQLE) is considered a metabolic oncogene, but its biological function and prognostic value in head and neck squamous cell carcinoma (HNSCC) remain unclear. We aimed to evaluate the role of SQLE in the occurrence and development of HNSCC through bioinformatics analysis, and validation experiments. Methods Transcriptomic, genomic, and clinical data from The Cancer Genome Atlas were used for pan-cancer analysis. SQLE expression in HNSCC was evaluated using Gene Expression Omnibus datasets and immunohistochemistry. The biological significance of SQLE in the tumor microenvironment (TME) of HNSCC was determined using TISCH, HuRI, LinkedOmics, and TIMER 2.0. The prognostic value of SQLE in HNSCC was analyzed using univariate Cox regression and Kaplan–Meier survival curves. Effect of SQLE on the Cal27 HNSCC cell line was evaluated using cell counting kit 8, wound healing, and EdU assays. Results SQLE was overexpressed and amplified in various cancers, including HNSCC. High SQLE expression promoted cell proliferation, associated with T stage in HNSCC patients. Copy number amplification and DNA demethylation contributed to high SQLE expression in HNSCC, which was associated with poor prognosis. SQLE was related to HNSCC TME, and its mRNA expression/copy number alterations were negatively correlated with the infiltration of CD8+ T cells, follicular helper T cells, and regulatory T cell infiltration and mast cell activation and positively correlated with the infiltration of M0 macrophages and resting mast cells in HNSCC. Conclusion SQLE was identified as a prognostic biomarker and a potential pharmaceutical target for HNSCC.

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TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

Cited by 664 publications

References 41 publications

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

High SQLE Expression and Gene Amplification Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma

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