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Published on: June 23, 2013
The Effect of Cuproptosis-Related Proteins on Macrophage Polarization in Mesothelioma is Revealed by scRNA-seq
Jia-Xin Xu1,2, Li-Jing Ma1, Li-Ying Tu1
1Faculty of Life Science and Technology, Kunming University of Science and Technology, Chenggong District, Kunming, 400042, China.
Abstract:
High invasiveness mesothelioma is a malignant tumor of the peritoneum or pleura. The effect of cuproptosis on mesothelioma (MESO) is still unknown, though. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets were used to identify differential genes linked to cuproptosis in mesothelioma. Multigene features were then created to assess the course of the disease. Use single-cell data and in vitro validation to uncover crucial gene regulation mechanisms. In MESO, we found nine differentially expressed genes linked to cuproptosis. Using univariate Cox and LASSO regression techniques, a 3-gene feature (P < 0.05) was created, showing a good predictive potential for survival time. According to the risk score, patients in the low-risk subset had a considerably greater survival rate than those in the high-risk subset (P = 0). The similar survival pattern and prediction performance are also seen in the validation queue. The findings of the drug sensitivity research indicate that in high-risk patients, vinblastine, paclitaxel, gefitinib, and erlotinib are sensitive medications (P < 0.05). Classical monocytes were identified as core cells connected to cuproptosis by the CellChat results. SLC31A1 is implicated in the positive regulation of M2 macrophage polarization, according to cell subtype analysis and in vitro confirmation. Genes linked to cuproptosis have a major influence on tumor immunity and can predict how MESO will progress.
Insights
Cuproptosis-related genes significantly impact mesothelioma (MESO) progression and immunity. A 3-gene signature effectively predicts patient survival and identifies potential drug sensitivities in high-risk MESO cases.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Mesothelioma (MESO) is an aggressive malignancy with poorly understood molecular underpinnings.
- The role of cuproptosis, a regulated form of cell death, in mesothelioma remains largely unexplored.
Purpose of the Study:
- To investigate the association between cuproptosis-related genes and mesothelioma.
- To identify novel biomarkers for predicting patient prognosis and therapeutic response in mesothelioma.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets to identify differentially expressed cuproptosis genes in mesothelioma.
- Developed a prognostic model using univariate Cox and LASSO regression with single-cell data and in vitro validation.
- Performed drug sensitivity analysis and cell-cell communication analysis (CellChat).
Main Results:
- Identified nine differentially expressed cuproptosis-related genes in mesothelioma.
- A 3-gene signature demonstrated significant predictive potential for patient survival (P < 0.05).
- Low-risk patients exhibited significantly better survival rates than high-risk patients (P = 0).
- High-risk patients showed sensitivity to vinblastine, paclitaxel, gefitinib, and erlotinib.
- Classical monocytes were identified as key cells involved in cuproptosis, with SLC31A1 linked to M2 macrophage polarization.
Conclusions:
- Cuproptosis-related genes play a crucial role in mesothelioma tumor immunity and progression.
- The developed 3-gene signature serves as a reliable prognostic tool for mesothelioma.
- Findings provide insights into targeted therapies for high-risk mesothelioma patients.
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