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

二硫代蛋白酶凋亡相关基因的综合分析:透明细胞肾细胞癌的预后模型构建和肿瘤微环境表征

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作者:Bocun Yi, Xifeng Wei, Dongze Liu, Liwei Jing, Shengxian Xu, Man Zhang, Zhengxin Liang, Ranlu Liu, Zhihong Zhang

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.

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.

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.

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