A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification
IntroductionClear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.815223/full |
| _version_ | 1818952611172188160 |
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| author | Jiyue Wu Jiyue Wu Zejia Sun Zejia Sun Qing Bi Qing Bi Wei Wang Wei Wang |
| author_facet | Jiyue Wu Jiyue Wu Zejia Sun Zejia Sun Qing Bi Qing Bi Wei Wang Wei Wang |
| author_sort | Jiyue Wu |
| collection | DOAJ |
| description | IntroductionClear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC.Materials and MethodsThe mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay.ResultsIn this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC.ConclusionIn this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment. |
| first_indexed | 2024-12-20T09:53:08Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T09:53:08Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8fcfcbb09bb2499fb906019b3a9d89732022-12-21T19:44:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011210.3389/fonc.2022.815223815223A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental VerificationJiyue Wu0Jiyue Wu1Zejia Sun2Zejia Sun3Qing Bi4Qing Bi5Wei Wang6Wei Wang7Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaIntroductionClear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC.Materials and MethodsThe mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay.ResultsIn this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC.ConclusionIn this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.815223/fullclear cell renal cell carcinomaferroptosisstratified modelindividualized treatmentbioinformatics |
| spellingShingle | Jiyue Wu Jiyue Wu Zejia Sun Zejia Sun Qing Bi Qing Bi Wei Wang Wei Wang A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification Frontiers in Oncology clear cell renal cell carcinoma ferroptosis stratified model individualized treatment bioinformatics |
| title | A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification |
| title_full | A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification |
| title_fullStr | A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification |
| title_full_unstemmed | A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification |
| title_short | A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification |
| title_sort | ferroptosis related genes model allows for prognosis and treatment stratification of clear cell renal cell carcinoma a bioinformatics analysis and experimental verification |
| topic | clear cell renal cell carcinoma ferroptosis stratified model individualized treatment bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.815223/full |
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