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一个新视角:解析在肾透明细胞癌中二硫键错配特征的异常和临床意义。

A new perspective: deciphering the aberrance and clinical implication of disulfidptosis signatures in clear cell renal cell carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.

Department of neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.

出版信息

Aging (Albany NY). 2024 Jun 10;16(11):10033-10062. doi: 10.18632/aging.205916.


DOI:10.18632/aging.205916
PMID:38862242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11210246/
Abstract

Recent research has discovered disulfidptosis as a form of programmed cell death characterized by disulfide stress. However, its significance in clear cell renal cell carcinoma (ccRCC) remains unclear. To investigate this, data from The Cancer Genome Atlas were collected and used to identify ccRCC subgroups. Unsupervised clustering was employed to determine ccRCC heterogeneity. The mutation landscape and immune microenvironment of the subgroups were analyzed. The Disulfidptosis-Related Score was calculated using the LASSO-penalized Cox regression algorithm. The E-MATB-1980 cohort was used to validate the signature. The role of SLC7A11 in ccRCC metastasis was explored using western blotting and Transwell assays. Disulfidptosis-related genes are commonly downregulated in cancers and are linked to hypermethylation and copy number variation. The study revealed that ccRCC is divided into two sub-clusters: the disulfidptosis-desert sub-cluster, which is associated with a poor prognosis, a higher mutation frequency, and an immunosuppressive microenvironment. A 14-gene prognostic model was developed using differentially expressed genes and was validated in the E-MATB-1980 cohort. The low-risk group demonstrated longer overall and disease-free survival and responded better to targeted immunotherapy. Results from experiments identified SLC7A11 as a key participant in ccRCC metastasis.

摘要

最近的研究发现,二硫键细胞程序性死亡是一种由二硫键应激引起的细胞程序性死亡形式。然而,它在透明细胞肾细胞癌(ccRCC)中的意义尚不清楚。为了研究这一点,从癌症基因组图谱中收集了数据,并用于鉴定 ccRCC 亚组。采用无监督聚类来确定 ccRCC 的异质性。分析了亚组的突变景观和免疫微环境。使用 LASSO 惩罚 Cox 回归算法计算了二硫键细胞程序性死亡相关评分。使用 E-MATB-1980 队列验证了特征。使用 Western blot 和 Transwell 测定探索了 SLC7A11 在 ccRCC 转移中的作用。二硫键细胞程序性死亡相关基因在癌症中通常下调,与 hypermethylation 和拷贝数变异有关。研究表明,ccRCC 分为两个亚组:二硫键细胞程序性死亡沙漠亚组,与预后不良、突变频率较高和免疫抑制微环境有关。使用差异表达基因开发了一个 14 基因预后模型,并在 E-MATB-1980 队列中进行了验证。低风险组的总生存期和无病生存期更长,对靶向免疫治疗的反应更好。实验结果确定 SLC7A11 是 ccRCC 转移的关键参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/24b32330afb6/aging-16-205916-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/24b32330afb6/aging-16-205916-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/996a1247cb42/aging-16-205916-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/0143b038e187/aging-16-205916-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/cb12967baae8/aging-16-205916-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/27c1dd30382e/aging-16-205916-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/abdcfaad46f2/aging-16-205916-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/852c3e663cb1/aging-16-205916-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/3362c307c74f/aging-16-205916-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/8ea76668bd43/aging-16-205916-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3345/11210246/24b32330afb6/aging-16-205916-g013.jpg

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引用本文的文献

[1]
Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.

Biomark Res. 2025-2-26

本文引用的文献

[1]
Multiomics characterization and verification of clear cell renal cell carcinoma molecular subtypes to guide precise chemotherapy and immunotherapy.

Imeta. 2023-11-16

[2]
An Integrated Machine Learning Framework Identifies Prognostic Gene Pair Biomarkers Associated with Programmed Cell Death Modalities in Clear Cell Renal Cell Carcinoma.

Front Biosci (Landmark Ed). 2024-3-21

[3]
Multi-omics identification of an immunogenic cell death-related signature for clear cell renal cell carcinoma in the context of 3P medicine and based on a 101-combination machine learning computational framework.

EPMA J. 2023-5-31

[4]
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J Transl Med. 2023-2-24

[5]
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis.

Nat Cell Biol. 2023-3

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Int J Mol Sci. 2022-8-31

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Clin Transl Med. 2022-5

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