Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma
Shiyong Xin,
Junjie Su,
Ruixin Li,
Qiong Cao,
Haojie Wang,
Zhihao Wei,
Chengliang Wang,
Chengdong Zhang,
Jianguo Zhang,
Zheng Zhang,
Guanyu Li,
Wang Qin
Affiliations
Shiyong Xin
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China; Corresponding author. Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, No. 636, Guan-lin Rd, Luo-long District, Luoyang, China.
Junjie Su
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
Ruixin Li
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
Qiong Cao
Department of Pathology, The Third Affiliated Hospital of Henan University of Science and Technology, 471003, China
Haojie Wang
Department of Central Laboratory, Zhengzhou University, Luoyang Central Hospital, Luoyang, 471003, China
Zhihao Wei
Department of Pathology, The Yiluo Hospital of Luoyang, The Teaching Hospital of Henan University of Science and Technology, Luoyang, 471023, China
Chengliang Wang
Department of Urology, Shangcheng County People's Hospital, Xinyang, 464000, China
Chengdong Zhang
Department of Urology, Xinxiang City First People's Hospital, Xinxiang, 453000, China
Jianguo Zhang
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
Zheng Zhang
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
Guanyu Li
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
Wang Qin
Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China
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.
