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pmid:37213288

Mitochondrial metabolic reprogramming-mediated immunogenic cell death reveals immune and prognostic features of clear cell renal cell carcinoma.

Lin Yang · Jing Xiong · Sheng Li · Xiaoqiang Liu · Wen Deng · Weipeng Liu · Bin Fu

Frontiers in oncology · 2023 doi:10.3389/fonc.2023.1146657

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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Mitochondrial metabolic reprogramming-mediated immunogenic cell death reveals immune and prognostic features of clear cell renal cell carcinoma.
doi
10.3389/fonc.2023.1146657
pmid
37213288
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[0]
Lin Yang
[1]
Jing Xiong
[2]
Sheng Li
[3]
Xiaoqiang Liu
[4]
Wen Deng
[5]
Weipeng Liu
[6]
Bin Fu
journal
Frontiers in oncology
year
2023
abstract
Background: Mitochondrial metabolic reprogramming (MMR)-mediated immunogenic cell death (ICD) is closely related to the tumor microenvironment (TME). Our purpose was to reveal the TME characteristics of clear cell renal cell carcinoma (ccRCC) by using them. Methods: Target genes were obtained by intersecting ccRCC differentially expressed genes (DEGs, tumor VS normal) with MMR and ICD-related genes. For the risk model, univariate COX regression and K-M survival analysis were used to identify genes most associated with overall survival (OS). Differences in the TME, function, tumor mutational load (TMB), and microsatellite instability (MSI) between high and low-risk groups were subsequently compared. Using risk scores and clinical variables, a nomogram was constructed. Predictive performance was evaluated by calibration plots and receiver operating characteristics (ROC). Results: We screened 140 DEGs, including 12 prognostic genes for the construction of risk models. We found that the immune score, immune cell infiltration abundance, and TMB and MSI scores were higher in the high-risk group. Thus, high-risk populations would benefit more from immunotherapy. We also identified the three genes (CENPA, TIMP1, and MYCN) as potential therapeutic targets, of which MYCN is a novel biomarker. Additionally, the nomogram performed well in both TCGA (1-year AUC=0.862) and E-MTAB-1980 cohorts (1-year AUC=0.909). Conclusions: Our model and nomogram allow accurate prediction of patients' prognoses and immunotherapy responses.
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Univariate COX regression and K-M survival analysis (screening criteria: p<0.01; GEPIA database, http://gepia.cancer-pku.cn/index.html) were performed using TCGA-KIRC expression and survival data to identify TGs most associated with overall survival (OS), which was then used to perform a least absolute shrinkage and selector operation analysis (LASSO) with the “glmnet” package.
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Univariate COX regression and K-M survival analysis (screening criteria: p<0.01; GEPIA database, http://gepia.cancer-pku.cn/index.html) were performed using TCGA-KIRC expression and survival data to identify TGs most associated with overall survival (OS), which was then used to perform a least absolute shrinkage and selector operation analysis (LASSO) with the “glmnet” package.
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The study screened 140 differentially expressed target genes, including 12 prognostic genes, and found higher immune score, immune-cell infiltration, TMB, and MSI scores in the high-risk group.
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We screened 140 DEGs, including 12 prognostic genes for the construction of risk models. We found that the immune score, immune cell infiltration abundance, and TMB and MSI scores were higher in the high-risk group. Thus, high-risk populations would benefit more from immunotherapy.
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Univariate COX regression and K-M survival analysis (screening criteria: p<0.01; GEPIA database, http://gepia.cancer-pku.cn/index.html) were performed using TCGA-KIRC expression and survival data to identify TGs most associated with overall survival (OS), which was then used to perform a least absolute shrinkage and selector operation analysis (LASSO) with the “glmnet” package.
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Our purpose was to reveal the TME characteristics of clear cell renal cell carcinoma (ccRCC) by using them.\nMethods: Target genes were obtained by intersecting ccRCC differentially expressed genes (DEGs, tumor VS normal) with MMR and ICD-related genes. For the risk model, univariate COX regression and K-M survival analysis were used to identify genes most associated with overall survival (OS). Differences in the TME, function, tumor mutational load (TMB), and microsatellite instability (MSI) between high and low-risk groups were subsequently compared. Using risk scores and clinical variables, a nomogram was constructed. Predictive performance was evaluated by calibration plots and receiver operating characteristics (ROC).\nResults: We screened 140 DEGs, including 12 prognostic genes for the construction of risk models. We found that the immune score, immune cell infiltration abundance, and TMB and MSI scores were higher in the high-risk group. Thus, high-risk populations would benefit more from immunotherapy. We also identified the three genes (CENPA, TIMP1, and MYCN) as potential therapeutic targets, of which MYCN is a novel biomarker. 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