ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Yao, Wenchao; Liu, Xuxu; Tian, Maolan; Shen, Lu; Wang, Qiang; Zheng, Yi; Lv, Zhenyi; Hao, Chenjun; Xue, Dongbo; Meng, Xianmin

doi:10.1016/j.omto.2022.09.008

Cited by 13 publications

(5 citation statements)

References 48 publications

(46 reference statements)

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“…53 Enhanced monocyte invasion offers considerable protection against poor prognosis in cancer. 54 Herein, we demonstrated that the RR patients exhibited a larger proportion of B cell, CD8+ T cell, and monocyte contents, suggesting that these patients may be in a relatively active state of anti-tumor immune response. Among the aforementioned cells, monocytes were strongly and inversely associated with the risk score (R = À.4, p < .001).…”

Section: Discussionmentioning

confidence: 71%

“…Conversely, monocytes also accelerate tumor cytotoxicity, stimulate antigen‐presenting cells, and recruit NK cells to block tumor metastasis 53 . Enhanced monocyte invasion offers considerable protection against poor prognosis in cancer 54 . Herein, we demonstrated that the RR patients exhibited a larger proportion of B cell, CD8+ T cell, and monocyte contents, suggesting that these patients may be in a relatively active state of anti‐tumor immune response.…”

Section: Discussionmentioning

confidence: 80%

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Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Zhang,

Wang,

2023

Environmental Toxicology

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Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy with high mortality and poor prognosis. Neutrophil extracellular traps (NETs) and the epithelial‐mesenchymal transition (EMT) significantly influence on the progression of various cancers. However, the underlying relevance of NETs‐ and EMT‐associated genes on the outcomes of patients with PAAD remains to be elucidated. Transcriptome RNA sequencing data, together with clinical information and single‐cell sequencing data of PAAD were collected from public databases. In the TCGA‐PAAD cohort, ssGSEA was used to calculate NET and EMT scores. WGCNA was used to determine the key gene modules. A risk model with eight NET‐ and EMT‐related genes (NERGs) was established using LASSO and multivariate Cox regression analysis. Patients in the reduced risk (RR) group showed better prognostic values compared with those in the elevated risk (ER) group. The prognostic model exhibited reliable and robust prediction when validated using an external database. The distributions of risk genes were explored in a single‐cell sequencing data set. Immune infiltration, immune cycle, and immune checkpoints were compared between the RR and ER groups. Moreover, potential chemotherapeutic drugs were examined. DCBLD2 was identified as a key gene in PAAD cell lines by qRT‐PCR, and was highly expressed in PAAD tissues. GSEA demonstrated that DCBLD2 induced the EMT. Transwell assays and western blotting showed that cell invasion and EMT induction were significantly reduced after DCBLD2 knockdown. Collectively, we constructed a prognosis model based on a NET and EMT gene signature, providing a valuable perspective for the prognostic evaluation and management of PAAD patient.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 80%

Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Zhang,

Wang,

2023

Environmental Toxicology

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“…The increase of tumor-associated macrophages (TAM) can accelerate the proliferation and invasion of ICC cells [48], which is closely associated with poor prognosis [49]. However, monocytes and macrophages play different roles in different tumors and tend to drive the tumor in either a good or bad direction, whereas in cholangiocarcinoma, monocyte in ltration is associated with a better prognosis [50]. Gamma delta T-cells are crucial in tumorigenesis and defense, and have a wide range of cytotoxicity to tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of Mendelian randomization and single-cell sequencing reveals the causal relationship between intrahepatic cholangiocarcinoma and chronotype-related genes

Liu,

Li,

et al. 2023

Preprint

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Background The tumor development is related to disruption of circadian rhythms. However, the causal relationship between chronotype and intrahepatic cholangiocarcinoma (ICC) and molecular mechanism of chronotype-related genes (CRGs) are vague. Methods Genetic summary statistics were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS and genome-wide association studies (GWAS) Catalog. Univariate Mendelian randomization (MR) analysis and sensitivity analysis were then performed. Subsequently, the CRGs were obtained based on the single nucleotide polymorphisms (SNPs) of chronotype for differential expression analysis between disease and control groups based on University of California, Santa Cruz (UCSC) Xena database, and the identification of hub genes via STRING database and immune infiltration analysis. Finally, the single-cell transcriptome dataset GSE138709 downloaded from Gene Expression Omnibus (GEO) database was used to analyze the relationship between hub genes and annotated cell types. The functional enrichment analysis, pseudotime analysis and cell communication analysis were also explored. Results The MR results revealed that chronotype was a protective factor causally related to ICC, and the reliability was illustrated by the sensitivity analysis. A total of 180 differentially expressed CRGs were acquired, including 101 up-regulated and 79 down-regulated in ICC. Of which, four genes were marked as hub genes based on protein-protein interaction network, namely IDH1, PEX13, DECR2 and PEX12. Moreover, a total of ten cell types were annotated in GSE138709, including T cells, malignant cells, macrophages, NK cells, dendritic cells, B cells, endothelial cells, cholangiocytes, hepatocytes and fibroblasts. Thereinto, NK cells and hepatocytes as key cells were remarkably discrepant between ICC and control samples. The expression of DECR2 and IDH1 in hepatocytes was higher in control group than in ICC group. Furthermore, hepatocytes might transform into cholangiocytes and malignant cells, and both hepatocytes and NK cells interacted strongly with macrophages. Conclusion Our study supported a causal relationship between chronotype and ICC, and provided the theoretical basis and reference value for research on MR.

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“…Yao et al [137] utilized RNA-seq to examine the number of immune cells and their impact on the prognosis of CCA, and to assess the function of different immune cell infiltrates in CCA. The scRNA-seq dataset (GEO: GSE138709) was used to identify the variety and heterogeneity of several cell subsets in CCA tissues.…”

Section: Main Signaling Pathwaysmentioning

confidence: 99%

Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy

Scimeca

Rovella

Palumbo

et al. 2023

Cancers

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Cholangiocarcinoma is a highly aggressive cancer arising from the bile ducts. The limited effectiveness of conventional therapies has prompted the search for new approaches to target this disease. Recent evidence suggests that distinct programmed cell death mechanisms, namely, apoptosis, ferroptosis, pyroptosis and necroptosis, play a critical role in the development and progression of cholangiocarcinoma. This review aims to summarize the current knowledge on the role of programmed cell death in cholangiocarcinoma and its potential implications for the development of novel therapies. Several studies have shown that the dysregulation of apoptotic signaling pathways contributes to cholangiocarcinoma tumorigenesis and resistance to treatment. Similarly, ferroptosis, pyroptosis and necroptosis, which are pro-inflammatory forms of cell death, have been implicated in promoting immune cell recruitment and activation, thus enhancing the antitumor immune response. Moreover, recent studies have suggested that targeting cell death pathways could sensitize cholangiocarcinoma cells to chemotherapy and immunotherapy. In conclusion, programmed cell death represents a relevant molecular mechanism of pathogenesis in cholangiocarcinoma, and further research is needed to fully elucidate the underlying details and possibly identify therapeutic strategies.

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ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Cited by 13 publications

References 48 publications

Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Comprehensive analyses and experimental verification of NETs and an EMT gene signature for prognostic prediction, immunotherapy, and chemotherapy in pancreatic adenocarcinoma

Comprehensive analysis of Mendelian randomization and single-cell sequencing reveals the causal relationship between intrahepatic cholangiocarcinoma and chronotype-related genes

Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy

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