Identification of cuproptosis-associated subtypes and signature genes for diagnosis and risk prediction of Ulcerative colitis based on machine learning

Tang, Dadong; Pu, Baoping; Liu, Shiru; Li, Hongyan

doi:10.3389/fimmu.2023.1142215

Cited by 2 publications

(2 citation statements)

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“…Researchers have identified several cuproptosis-related genes (CRGs) that contribute to disease progression, with a primary focus on tumor advancement, which may impact the tumor immune microenvironment and predict the effectiveness of immunotherapy (11)(12)(13)(14). Additionally, studies have indicated that CRG signatures are closely associated with certain inflammation-related conditions, including inflammatory bowel disease (15), ulcerative colitis (16,17), and Alzheimer's disease (18,19). Considering that sepsis is characterized by a systemic inflammatory response, we hypothesize that cuproptosis may play a role in sepsis.…”

Section: Introductionmentioning

confidence: 99%

Identification and experimental validation of cuproptosis regulatory program in a sepsis immune microenvironment through a combination of single-cell and bulk RNA sequencing

Zhao,

Guo,

2024

Front. Immunol.

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BackgroundIn spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk model to diagnose and predict the risk of sepsis. In addition, the cuproptosis-related genes were identified for targeted therapy.MethodsSingle-cell sequencing analyses were used to characterize the cuproptosis activity score (CuAS) and intercellular communications in sepsis. Differential cuproptosis-related genes (CRGs) were identified in conjunction with single-cell and bulk RNA sequencing. LASSO and Cox regression analyses were employed to develop a risk model. Three external cohorts were conducted to assess the model’s accuracy. Differences in immune infiltration, immune cell subtypes, pathway enrichment, and the expression of immunomodulators were further evaluated in distinct groups. Finally, various in-vitro experiments, such as flow cytometry, Western blot, and ELISA, were used to explore the role of LST1 in sepsis.ResultsScRNA-seq analysis demonstrated that CuAS was highly enriched in monocytes and was closely related to the poor prognosis of sepsis patients. Patients with higher CuAS exhibited prominent strength and numbers of cell–cell interactions. A total of five CRGs were identified based on the LASSO and Cox regression analyses, and a CRG-based risk model was established. The lower riskScore cohort exhibited enhanced immune cell infiltration, elevated immune scores, and increased expression of immune modulators, indicating the activation of an antibacterial response. Ultimately, in-vitro experiments demonstrated that LST1, a key gene in the risk model, was enhanced in the macrophage in response to LPS, which was closely related to the decrease of macrophage survival rate, the enhancement of apoptosis and oxidative stress injury, and the imbalance of the M1/M2 phenotype.ConclusionsThis study constructed a cuproptosis-related risk model to accurately predict the prognosis of sepsis. We further characterized the cuproptosis-related gene LST1 to provide a theoretical framework for sepsis therapy.

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