A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration
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 t...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-08-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-021-02096-3 |
| _version_ | 1818365430795862016 |
|---|---|
| author | Jiao-chen Luan Teng-yue Zeng Qi-jie Zhang De-run Xia Rong Cong Liang-yu Yao Le-bin Song Xiang Zhou Xuan Zhou Xiang Chen Jia-dong Xia Ning-hong Song |
| author_facet | Jiao-chen Luan Teng-yue Zeng Qi-jie Zhang De-run Xia Rong Cong Liang-yu Yao Le-bin Song Xiang Zhou Xuan Zhou Xiang Chen Jia-dong Xia Ning-hong Song |
| author_sort | Jiao-chen Luan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T22:20:09Z |
| format | Article |
| id | doaj.art-33d8073a1b754a84922f8ec792ac784a |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T22:20:09Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-33d8073a1b754a84922f8ec792ac784a2022-12-21T23:29:24ZengBMCCancer Cell International1475-28672021-08-0121111710.1186/s12935-021-02096-3A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltrationJiao-chen Luan0Teng-yue Zeng1Qi-jie Zhang2De-run Xia3Rong Cong4Liang-yu Yao5Le-bin Song6Xiang Zhou7Xuan Zhou8Xiang Chen9Jia-dong Xia10Ning-hong Song11Department of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract 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.https://doi.org/10.1186/s12935-021-02096-3Bladder cancerFerroptosisPrognosisImmune infiltrationTFRC |
| spellingShingle | Jiao-chen Luan Teng-yue Zeng Qi-jie Zhang De-run Xia Rong Cong Liang-yu Yao Le-bin Song Xiang Zhou Xuan Zhou Xiang Chen Jia-dong Xia Ning-hong Song A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration Cancer Cell International Bladder cancer Ferroptosis Prognosis Immune infiltration TFRC |
| title | A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration |
| title_full | A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration |
| title_fullStr | A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration |
| title_full_unstemmed | A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration |
| title_short | A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration |
| title_sort | novel signature constructed by ferroptosis associated genes fags for the prediction of prognosis in bladder urothelial carcinoma blca and associated with immune infiltration |
| topic | Bladder cancer Ferroptosis Prognosis Immune infiltration TFRC |
| url | https://doi.org/10.1186/s12935-021-02096-3 |
| work_keys_str_mv | AT jiaochenluan anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT tengyuezeng anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT qijiezhang anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT derunxia anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT rongcong anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT liangyuyao anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT lebinsong anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xiangzhou anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xuanzhou anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xiangchen anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT jiadongxia anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT ninghongsong anovelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT jiaochenluan novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT tengyuezeng novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT qijiezhang novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT derunxia novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT rongcong novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT liangyuyao novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT lebinsong novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xiangzhou novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xuanzhou novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT xiangchen novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT jiadongxia novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration AT ninghongsong novelsignatureconstructedbyferroptosisassociatedgenesfagsforthepredictionofprognosisinbladderurothelialcarcinomablcaandassociatedwithimmuneinfiltration |