Dataset Information

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

ABSTRACT:

Background

Disulfidptosis, a form of cell death induced by abnormal intracellular accumulation of disulfides, is a newly recognized variety of cell death. Clear cell renal cell carcinoma (ccRCC) is a usual urological tumor that poses serious health risks. There are few studies of disulfidptosis-related genes (DRGs) in ccRCC so far.

Methods

The expression, transcriptional variants, and prognostic role of DRGs were assessed. Based on DRGs, consensus unsupervised clustering analysis was performed to stratify ccRCC patients into various subtypes and constructed a DRG risk scoring model. Patients were stratified into high or low-risk groups by this model. We focused on assessing the discrepancy in prognosis, TME, chemotherapeutic susceptibility, and landscape of immune between the two risk groups. Finally, we validated the expression and explored the biological function of the risk scoring gene FLRT3 through in vitro experiments.

Results

The different subtypes had significantly different gene expression, immune, and prognostic landscapes. In the two risk groups, the high-risk group had higher TME scores, more significant immune cell infiltration, and a higher probability of benefiting from immunotherapy, but had a worse prognosis. There were also remarkable differences in chemotherapeutic susceptibility between the two risk groups. In ccRCC cells, the expression of FLRT3 was shown to be lower and its overexpression caused a decrease in cell proliferation and metastatic capacity.

Conclusions

Starting from disulfidptosis, we established a new risk scoring model which can provide new ideas for doctors to forecast patient survival and determine clinical treatment plans.

SUBMITTER: Yi B

PROVIDER: S-EPMC10929811 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

Yi Bocun B Wei Xifeng X Liu Dongze D Jing Liwei L Xu Shengxian S Zhang Man M Liang Zhengxin Z Liu Ranlu R Zhang Zhihong Z

Aging 20240214 4

<h4>Background</h4>Disulfidptosis, a form of cell death induced by abnormal intracellular accumulation of disulfides, is a newly recognized variety of cell death. Clear cell renal cell carcinoma (ccRCC) is a usual urological tumor that poses serious health risks. There are few studies of disulfidptosis-related genes (DRGs) in ccRCC so far.<h4>Methods</h4>The expression, transcriptional variants, and prognostic role of DRGs were assessed. Based on DRGs, consensus unsupervised clustering analysis ...[more]

PMID: 38358909

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Project description:BackgroundThe transcriptome public database and advances in biological discoveries contributed to significant progresses in identifying the drivers of cancer progression. Cellular senescence (CS) is considered as a leading factor resulting in cancer development. The purpose of this study was to explore the significance of CS-related genes in the molecular classification and survival outcome of clear cell renal cell carcinoma (ccRCC).MethodsCS-related genes were obtained from the CellAge database, and patients from TCGA-KIRC dataset and ICGC dataset were clustered by ConsesusClusterPlus. The characteristics of overall survival (OS), genomic variation, and tumor microenvironment (TME) of each cluster were analyzed. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was conducted to develop a CS-related risk model to score ccRCC patients and assess the risk scores in predicting patients' response to immunotherapy and chemotherapy. A nomogram based on the risk model was established to improve the risk stratification of patients.ResultsCcRCC was divided into three molecular subtypes based on CS-related genes. The three molecular phenotypes showed different OS and clinical manifestations, mutation patterns, and TME states. Five genes were obtained from nine differentially expressed CS-related genes in the three molecular subtypes to develop a risk model. Patients with ccRCC were divided into high- and low-risk subgroups. The former showed an unfavorable OS, with a significantly higher genomic variation rate, TME score, and numerous immune checkpoint expressions when compared to the low-risk subgroup. Risk score reflected the response of patients to axitinib, bortezomib, sorafenib, sunitinib, and temsirolimus.ConclusionsIn general, CS-related genes divided ccRCC into three molecular subtypes with distinct OS, mutation patterns, and TME states. The risk model based on the five CS-related genes can predict the prognosis and therapeutic outcome of ccRCC patients, providing a theoretical basis for further study on the molecular mechanism of CS-related ccRCC.

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Dataset Information

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

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