Jiao-Chen Luan1, Teng-Yue Zeng1, Qi-Jie Zhang1, De-Run Xia2, Rong Cong1, Liang-Yu Yao1, Le-Bin Song3, Xiang Zhou1, Xuan Zhou1, Xiang Chen4, Jia-Dong Xia5, Ning-Hong Song6,7. 1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. 3. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 4. Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China. 5. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. dongjiaxianjmu@sina.com. 6. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, China. songninghong_urol@163.com. 7. The Affiliated Kezhou People's Hospital of Nanjing Medical University, Kezhou, Xinjiang, China. songninghong_urol@163.com.
Abstract
BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.
BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCApatients.
Authors: Marko Babjuk; Andreas Böhle; Maximilian Burger; Otakar Capoun; Daniel Cohen; Eva M Compérat; Virginia Hernández; Eero Kaasinen; Joan Palou; Morgan Rouprêt; Bas W G van Rhijn; Shahrokh F Shariat; Viktor Soukup; Richard J Sylvester; Richard Zigeuner Journal: Eur Urol Date: 2016-06-17 Impact factor: 20.096
Authors: Tian C Zhou; Alexander I Sankin; Steven A Porcelli; David S Perlin; Mark P Schoenberg; Xingxing Zang Journal: Urol Oncol Date: 2016-11-03 Impact factor: 3.498
Authors: Marko Babjuk; Willem Oosterlinck; Richard Sylvester; Eero Kaasinen; Andreas Böhle; Juan Palou-Redorta Journal: Eur Urol Date: 2008-04-30 Impact factor: 20.096