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Abstract：
Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.
摘要：
二硫化物下垂，一种新发现的由细胞内二硫化物化合物过度积累引起的细胞死亡模式，与肿瘤的发展密切相关。本研究主要探讨肾透明细胞癌(ccRCC)与肾透明细胞癌(ccRCC)的关系。首先,显示了ccRCC中二硫凋亡相关基因（DRGs）的特征，其中包括数量变异(CNV)，单核苷酸变异（SNV），DNA甲基化，mRNA表达和基因突变。然后，通过基于DRGs的无监督聚类将ccRCC样本分为三个聚类。评估了三个集群之间的存活和途径富集差异。随后，通过单变量Cox筛选三个簇中的差异表达基因（DEGs），拉索,和多变量Cox分析，获得了五个关键DEG。根据五个关键DEG,将ccRCC样品重新分类为两个基因组，并研究了两个基因组之间的存活差异和免疫细胞浸润。下一步,根据五个关键DEGs的PCA评分将ccRCC样本分为两组，即PCA评分高组(HPSG)和PCA评分低组(LPSG)。在此基础上,生存预后的差异，免疫细胞浸润和与免疫检查点的相关性，比较了HPSG和LPSG对靶向药物的敏感性差异.HPSG中四个免疫检查点的表达水平高于LPSG，而LPSG对靶向药物治疗比HPSG更敏感。最后,对HDAC4的验证实验表明，HDAC4可以增加ccRCC细胞的增殖和集落形成能力。
