{"title":"Multi-omic analysis constructs ferroptosis subtypes and risk signature and reveals that PEBP1 is an important tumor suppressor in kidney cancer.","authors":"Shuaiqi Chen, Xizi Cheng, Zeyu Li, Huijun Fan, Xiangdong Xue, Kuo Ma, Jingxian Li, Feng Zhu","doi":"10.1007/s13577-025-01303-x","DOIUrl":null,"url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent type of regulated cell death driven by excessive lipid peroxidation, plays an important role in natural tumor suppression. In this study, we identified 23 ferroptosis-related genes associated with prognosis in kidney cancer datasets. Based on the expression profiles of these genes, we classified kidney cancer into four distinct subtypes and constructed a 9-gene risk score to predict the prognosis of patients. Our analysis revealed that patients classified into group III and those in the low-risk group demonstrated significantly better survival probability. Moreover, the risk score exhibited strong predictive accuracy for the prognosis of kidney renal clear-cell carcinoma (KIRC) patients. Among the identified genes, PEBP1 showed elevated expression in both subtype III and the low-risk group, suggesting that it may act as a critical tumor suppressor. To further evaluate this, we examined PEBP1 expression patterns and their clinical correlations using TCGA-KIRC and KIRP cohorts. The results indicated that PEBP1 deletion was strongly associated with poor prognosis, while reduced PEBP1 expression correlated with advanced disease progression in both KIRC and KIRP patients. Functional enrichment analysis suggested that PEBP1 may be involved in pathways related to fatty acid metabolism and oxidative phosphorylation. Experimental validation supported these findings, showing that PEBP1 overexpression suppressed the proliferation and migration of kidney cancer cells. Additionally, PEBP1 promoted the accumulation of lipid reactive oxygen species (ROS), an effect that was reversed by a ferroptosis inhibitor. Conversely, silencing PEBP1 counteracted the lipid ROS induced by RSL4, a ferroptosis activator. In summary, our results demonstrate that PEBP1 functions as a potential tumor suppressor in kidney cancer and may serve as a promising prognostic biomarker and therapeutic target.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 6","pages":"173"},"PeriodicalIF":3.1000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13577-025-01303-x","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Ferroptosis, an iron-dependent type of regulated cell death driven by excessive lipid peroxidation, plays an important role in natural tumor suppression. In this study, we identified 23 ferroptosis-related genes associated with prognosis in kidney cancer datasets. Based on the expression profiles of these genes, we classified kidney cancer into four distinct subtypes and constructed a 9-gene risk score to predict the prognosis of patients. Our analysis revealed that patients classified into group III and those in the low-risk group demonstrated significantly better survival probability. Moreover, the risk score exhibited strong predictive accuracy for the prognosis of kidney renal clear-cell carcinoma (KIRC) patients. Among the identified genes, PEBP1 showed elevated expression in both subtype III and the low-risk group, suggesting that it may act as a critical tumor suppressor. To further evaluate this, we examined PEBP1 expression patterns and their clinical correlations using TCGA-KIRC and KIRP cohorts. The results indicated that PEBP1 deletion was strongly associated with poor prognosis, while reduced PEBP1 expression correlated with advanced disease progression in both KIRC and KIRP patients. Functional enrichment analysis suggested that PEBP1 may be involved in pathways related to fatty acid metabolism and oxidative phosphorylation. Experimental validation supported these findings, showing that PEBP1 overexpression suppressed the proliferation and migration of kidney cancer cells. Additionally, PEBP1 promoted the accumulation of lipid reactive oxygen species (ROS), an effect that was reversed by a ferroptosis inhibitor. Conversely, silencing PEBP1 counteracted the lipid ROS induced by RSL4, a ferroptosis activator. In summary, our results demonstrate that PEBP1 functions as a potential tumor suppressor in kidney cancer and may serve as a promising prognostic biomarker and therapeutic target.
期刊介绍:
Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well.
Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format.
Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.