Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer

Deng, Cheng; Deng, Guofei; Chu, Hongwu; Chen, Songyao; Chen, Xiancong; Li, Xing; He, Yulong; Sun, Chunhui; Zhang, Changhua

doi:10.3389/fimmu.2023.1140328

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…GC is a common gastrointestinal malignancy with a poor prognosis worldwide (Deng et al, 2023). Recently, several studies have evaluated the prognostic value of biomarkers for GC (Wang et al, 2023; tissues.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of HIGD1B induces mitochondria‐mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways

Chen,

Sun,

2024

Drug Development Research

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Gastric cancer (GC) is one of the most common malignancies worldwide. Hypoxia‐inducible domain (HIGD) family members (e.g., HIGD1A) have been linked to tumor progression. However, the role of HIGD1B (another HIGD family member) in GC has yet to be fully understood. Based on data from TCGA_GC, GSE65801, and GSE65801 data sets, HIGD1B levels were evaluated in normal and GC tissues. Next, HIGD1B levels were validated by reverse transcription‐quantitative PCR and western blot analysis analyses. Meanwhile, patients with GC in the TCGA_GC cohort were grouped into high‐ and low‐HIGD1B level groups, and overall survival, functional enrichment, and immune infiltration were analyzed. Additionally, gain‐ and loss‐of‐function experiments were performed to determine the function of HIGD1B in GC cells. Compared to normal controls, HIGD1B mRNA levels were significantly elevated in GC tissues. Moreover, high HIGD1B levels may be an independent indicator of poor prognosis in patients with GC. Additionally, high HIGD1B levels were correlated with high stromal and ESTIMATE scores and elevated expression of immune checkpoints in patients with GC. Functional analyses showed that HIGD1B deficiency notably suppressed GC cell proliferation, migration, and invasion. Moreover, HIGD1B deficiency significantly induced mitochondria‐mediated apoptosis in GC cells by inactivating Akt and ERK pathways. Collectively, HIGD1B may predict the prognosis of patients with GC and may function as an oncogene in GC. These findings suggest that HIGD1B may serve as a prognostic biomarker and potential therapeutic target in GC.

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Section: Discussionmentioning

confidence: 99%

Downregulation of HIGD1B induces mitochondria‐mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways

Chen,

Sun,

2024

Drug Development Research

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“…We visualized the above cell subgroups in the form of UMAP [ 23 ]. Additionally, we employed six algorithms to score gene sets in the single-cell dataset: AUCell [ 24 ], Ucells [ 25 ], Singscore [ 26 ], ssGSEA [ 27 ], addmodulescore [ 28 , 29 ], and scoring [ 17 ]. The scoring value is the sum of scores from the previous five methods and serves to assess the overall distribution of parthanatos gene set scores more stably and comprehensively.…”

Section: Methodsmentioning

confidence: 99%

Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer

Qiao,

Sun,

Ren

et al. 2024

Aging

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Background: Parthanatos is a novel programmatic form of cell death based on DNA damage and PARP-1 dependency. Nevertheless, its specific role in the context of gastric cancer (GC) remains uncertain. Methods: In this study, we integrated multi-omics algorithms to investigate the molecular characteristics of parthanatos in GC. A series of bioinformatics algorithms were utilized to explore clinical heterogeneity of GC and further predict the clinical outcomes. Results: Firstly, we conducted a comprehensive analysis of the omics features of parthanatos in various human tumors, including genomic mutations, transcriptome expression, and prognostic relevance. We successfully identified 7 cell types within the GC microenvironment: myeloid cell, epithelial cell, T cell, stromal cell, proliferative cell, B cell, and NK cell. When compared to adjacent non-tumor tissues, single-cell sequencing results from GC tissues revealed elevated scores for the parthanatos pathway across multiple cell types. Spatial transcriptomics, for the first time, unveiled the spatial distribution characteristics of parthanatos signaling. GC patients with different parthanatos signals often exhibited distinct immune microenvironment and metabolic reprogramming features, leading to different clinical outcomes. The integration of parthanatos signaling and clinical indicators enabled the creation of novel survival curves that accurately assess patients’ survival times and statuses. Conclusions: In this study, the molecular characteristics of parthanatos’ unicellular and spatial transcriptomics in GC were revealed for the first time. Our model based on parthanatos signals can be used to distinguish individual heterogeneity and predict clinical outcomes in patients with GC.

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“…We curated a collection of 32 disulfidoptosis-related genes, integral to cancer research, constituting the disulfidoptosis-related gene set. Leveraging the GSE149655 dataset, we harnessed algorithms including AUCell, Ucell, singscore, ssGSEA, and AddModuleScore (Add) to compute gene set scores for the disulfidoptosis-related gene sets ( 15 , 16 ). Subsequently, the outcomes of these five gene set scores were amalgamated and standardized for the purpose of Scoring analysis.…”

Section: Methodsmentioning

confidence: 99%

Elaboration and validation of a prognostic signature associated with disulfidoptosis in lung adenocarcinoma, consolidated with integration of single-cell RNA sequencing and bulk RNA sequencing techniques

He,

Tang,

Yang

et al. 2023

Front. Immunol.

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BackgroundLung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), remains a pervasive global public health concern. Disulfidoptosis, a nascent form of regulated cell death (RCD), presents an emerging field of inquiry. Currently, investigations into disulfidoptosis are in their initial stages. Our undertaking sought to integrate single-cell RNA sequencing (scRNA-seq) in conjunction with traditional bulk RNA sequencing (bulk RNA-seq) methodologies, with the objective of delineating genes associated with disulfidoptosis and subsequently prognosticating the clinical outcomes of LUAD patients.MethodsInitially, we conducted an in-depth examination of the cellular composition disparities existing between LUAD and normal samples using scRNA-seq data sourced from GSE149655. Simultaneously, we scrutinized the expression patterns of disulfidoptosis-associated gene sets across diverse cell types. Subsequently, leveraging the bulk RNA-seq data, we formulated disulfidoptosis-related prognostic risk signatures (DRPS) employing LASSO-Cox regression. This was accomplished by focusing on genes implicated in disulfidoptosis that exhibited differential expression within endothelial cells (ECs). Sequentially, the robustness and precision of the DRPS model were rigorously verified through both internal and external validation datasets. In parallel, we executed single-cell trajectory analysis to delve into the differentiation dynamics of ECs. Concluding our study, we undertook a comprehensive investigation encompassing various facets. These included comparative assessments of enrichment pathways, clinicopathological parameters, immune cell abundance, immune response-associated genes, impacts of immunotherapy, and drug predictions among distinct risk cohorts.ResultsThe scrutiny of scRNA-seq data underscored discernible disparities in cellular composition between LUAD and normal samples. Furthermore, disulfidoptosis-associated genes exhibited marked discrepancies within endothelial cells (ECs). Consequently, we formulated the Disulfidoptosis-Related Prognostic Signature (DRPS) to facilitate prognostic prediction. The prognostic nomogram based on the risk score effectively demonstrated DRPS’s robust capacity to prognosticate survival outcomes. This assertion was corroborated by rigorous assessments utilizing both internal and external validation sets, thus affirming the commendable predictive accuracy and enduring stability of DRPS. Functional enrichment analysis shed light on the significant correlation of DRPS with pathways intrinsic to the cell cycle. Subsequent analysis unveiled correlations between DRPS and gene mutations characteristic of LUAD, as well as indications of an immunosuppressive status. Through drug prediction, we explored potential therapeutic agents for low-risk patients. Concluding our investigation, qRT-PCR experiments confirmed the heightened expression levels of EPHX1, LDHA, SHC1, MYO6, and TLE1 in lung cancer cell lines.

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Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer

Cited by 6 publications

References 41 publications

Downregulation of HIGD1B induces mitochondria‐mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways

Downregulation of HIGD1B induces mitochondria‐mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways

Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer

Elaboration and validation of a prognostic signature associated with disulfidoptosis in lung adenocarcinoma, consolidated with integration of single-cell RNA sequencing and bulk RNA sequencing techniques

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