Development of a Prognostic Signature Based on Single-Cell RNA Sequencing Data of Immune Cells in Intrahepatic Cholangiocarcinoma

Su, Miao; Qiao, Kuangyuan; Xie, Xing; Zhu, Xinying; Fulai, Gao; Li, Changjuan; Zhao, Dongqiang

doi:10.3389/fgene.2020.615680

Cited by 7 publications

(13 citation statements)

References 37 publications

(23 reference statements)

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“…Using a molecular approach, eCCAs were classified in metabolic, mesenchymal, proliferative, and immune classes, all characterized in terms of mutations and modulation of different actionable targets. Furthermore, the development of single-cell RNA sequencing now allows analysis of the discrete cell populations in the TRS, including CAFs [119] and immune response cells [120] , and to study in more detail the crosstalk between these cell milieus [121] . Finally, a recent study used nano liquid chromatography coupled to matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF) analysis to study the composition of the matrix (or matrisome) in CCA [122] .…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment and immunology of cholangiocarcinoma

Cadamuro¹,

Fabris²,

Zhang³

et al. 2022

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Cholangiocarcinoma (CCA), an aggressive tumor originating from both intra- and extra-hepatic biliary cells, represents an unmet need in liver oncology, as treatment remains largely unsatisfactory. A typical feature of CCA is the presence of a complex tumor microenvironment (TME) composed of neoplastic cells, a rich inflammatory infiltrate, and cancer-associated fibroblasts and desmoplastic matrix that makes it extremely chemoresistant to traditional chemotherapeutic drugs. In this review, we describe the cell populations within the TME, in particular those involved in the innate and adaptive immune response and how they interact with tumor cells and with matrix proteins. The TME is crucial for CCA to mount an immune escape response and is the battlefield where molecularly targeted therapies and immune therapy, particularly in combination, may actually prove their therapeutic value.

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Section: Discussionmentioning

confidence: 99%

Tumor microenvironment and immunology of cholangiocarcinoma

Cadamuro¹,

Fabris²,

Zhang³

et al. 2022

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“…PDGFD signaling in GBM was shown to induce IFN-g secretion by natural killer cells through the engagement of the human immunoreceptor NKp44 (33). Meanwhile, PDGFD was an important predictor gene for bladder cancer, renal clear cell carcinoma, and osteosarcoma (34)(35)(36). It has been found that TUBB3 was highly expressed in lung neuroendocrine carcinoma and medulloblastoma, which was associated with positive lymphatic permeation (37,38).…”

Section: Discussionmentioning

confidence: 99%

An Immunity-Related Gene Model Predicts Prognosis in Cholangiocarcinoma

Guo

Qian

et al. 2022

Front. Oncol.

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The prognosis of patients with cholangiocarcinoma (CCA) is closely related to both immune cell infiltration and mRNA expression. Therefore, we aimed at conducting multi-immune-related gene analyses to improve the prediction of CCA recurrence. Immune-related genes were selected from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Immunology Database and Analysis Portal (ImmPort). The least absolute shrinkage and selection operator (LASSO) regression model was used to establish the multi-gene model that was significantly correlated with the recurrence-free survival (RFS) in two test series. Furthermore, compared with single genes, clinical characteristics, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS), the 8-immune-related differentially expressed genes (8-IRDEGs) signature had a better prediction value. Moreover, the high-risk subgroup had a lower density of B-cell, plasma, B-cell naïve, CD8+ T-cell, CD8+ T-cell naïve, and CD8+ T-cell memory infiltration, as well as more severe immunosuppression and higher mutation counts. In conclusion, the 8-IRDEGs signature was a promising biomarker for distinguishing the prognosis and the molecular and immune features of CCA, and could be beneficial to the individualized immunotherapy for CCA patients.

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“…Dimension reduction analysis was performed with the Seurat “RunPCA” function, and non-linear dimensional reduction was performed with the Seurat “RunUMAP” function. The tSNE analysis was used for dimension reduction to determine the cell populations and for visualization of the gene expression ( 14 ). The FindClusters function was performed with a resolution of 0.5, and the RunTSNE function was used to generate clusters.…”

Section: Methodsmentioning

confidence: 99%

“…Miao Su et al. established nine-prognosis-related-genes (PRGs) by reanalyzing the ScRNA-seq ( 14 ). These genes included SLC16A3, BNIP3L, TPM2, CLEC11A, EREG, PMAIP1, CEBPB, A2M, and TUBA1B, which are correlated with ICC prognosis ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma

Yan

Long

et al. 2022

Front. Oncol.

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BackgroundIt has been shown that tumor-associated immune cells, particularly macrophages, play a fundamental role in the development and treatment response of intrahepatic cholangiocarcinoma (ICC). However, little is known about macrophages at the single cellular level of ICC patients.MethodsScRNA-seq from Zhang et al. was used in the present study to identify the genes differentially expressed in ICCs. Furthermore, transcriptomic data from TCGA datasets, IHC and flowcytometry from our cohort were used to confirm the findings. Kaplan-Meier and TIDE scores were also used for prognostic analysis and ICB responses.ResultsA significant number of macrophages were found in ICCs as compared to adjacent tissues. We then extracted, processed, and classified the macrophages from the ICCs and adjacent tissues into 12 clusters. Significantly, the macrophages from the ICC exhibited an immunosuppressed state in terms of both signature gene expression and functional enrichment. Furthermore, our results indicate that, of the 10 selective tumor-promoting genes of macrophages, only MMP19 and SIRPα can predict ICB responses in ICCs. Although a higher expression of MMP19 and SIRPα predict a poor prognosis for ICCs without immunotherapy after surgery, patients with high SIRPα expression were more sensitive to immunotherapy, whereas those with high MMP19 expression were not sensitive to immunotherapy. To define the mechanisms, we found that SIRPαhi ICCs exhibited an increased enrichment KEGG pathway of leukocyte transendothelial migration and neutrophil extracellular trap formation. The increased immune cell infiltration will increase sensitivity to immunotherapy.ConclusionCollectively, macrophages are critical to the immune status of ICCs, and MMP19 and SIRPα can predict prognosis and ICB responses for ICCs.

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Development of a Prognostic Signature Based on Single-Cell RNA Sequencing Data of Immune Cells in Intrahepatic Cholangiocarcinoma

Cited by 7 publications

References 37 publications

Tumor microenvironment and immunology of cholangiocarcinoma

Tumor microenvironment and immunology of cholangiocarcinoma

An Immunity-Related Gene Model Predicts Prognosis in Cholangiocarcinoma

Identification of macrophage correlated biomarkers to predict the prognosis in patients with intrahepatic cholangiocarcinoma

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