Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients
Abstract Bladder cancer (BC) displays a huge phenotypic variation and widespread clinical outcomes, attributed to the high mutational heterogeneity of the disease. Mutational landscaping became integral to cancer patient management as it unveils driver genes and yields genotype–phenotype association...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-04363-z |
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| author | Taoufik Nedjadi Hifzur Ansari Muhammad A. Khan Naif Sannan Mubarak Al-Mansour Jaudah Al-Maghrabi Ashraf Dallol |
| author_facet | Taoufik Nedjadi Hifzur Ansari Muhammad A. Khan Naif Sannan Mubarak Al-Mansour Jaudah Al-Maghrabi Ashraf Dallol |
| author_sort | Taoufik Nedjadi |
| collection | DOAJ |
| description | Abstract Bladder cancer (BC) displays a huge phenotypic variation and widespread clinical outcomes, attributed to the high mutational heterogeneity of the disease. Mutational landscaping became integral to cancer patient management as it unveils driver genes and yields genotype–phenotype associations. This study aims to identify somatic mutations, their frequencies and their associations with clinical and prognostic outcomes in BC. Eighty-one BC patients were analyzed by next-generation sequencing using the Ion AmpliSeq Cancer Hotspots Panel v2. Bioinformatics analysis, correlation studies and Kaplan–Meier curve were used to evaluate the relationship between genes’ mutational status and patients’ clinical parameters and outcomes. Our results indicated that the BC cohort exhibited a higher mutation burden than the TCGA data. Mutations were identified in 46 out of 50 genes, including 21 novel mutations not previously reported in BC. The TP53 gene was mutated in 82.5% of the analyzed cohort, followed by PIK3 CA (45%), FGFR3 (43.75%) and APC (35%). TP53 mutations were associated with poor survival (p = 0.003) while the FGFR3 mutation group exhibited signs of good prognosis (p = 0.018). Bioinformatics highlighted significant gene interactions associated with poor prognosis. These findings underline the importance of identifying novel genetic mutations that could significantly improve prognostic stratification and expand therapeutic options for managing BC patients. |
| format | Article |
| id | doaj-art-3ca438d62c8c418ba4b56d261a0a66d9 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-3ca438d62c8c418ba4b56d261a0a66d92025-08-20T04:01:36ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-04363-zClinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patientsTaoufik Nedjadi0Hifzur Ansari1Muhammad A. Khan2Naif Sannan3Mubarak Al-Mansour4Jaudah Al-Maghrabi5Ashraf Dallol6King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health SciencesKing Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health SciencesCollege of Medicine, King Saud Bin Abdulaziz University for Health SciencesKing Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health SciencesPrincess Noorah Oncology Center, King Khalid Hospital, Ministry of National Guard-Health AffairsDepartment of Pathology, Faculty of Medicine, King Abdulaziz UniversityNoor Diagnostics and Discovery, King Abdullah University of Science and TechnologyAbstract Bladder cancer (BC) displays a huge phenotypic variation and widespread clinical outcomes, attributed to the high mutational heterogeneity of the disease. Mutational landscaping became integral to cancer patient management as it unveils driver genes and yields genotype–phenotype associations. This study aims to identify somatic mutations, their frequencies and their associations with clinical and prognostic outcomes in BC. Eighty-one BC patients were analyzed by next-generation sequencing using the Ion AmpliSeq Cancer Hotspots Panel v2. Bioinformatics analysis, correlation studies and Kaplan–Meier curve were used to evaluate the relationship between genes’ mutational status and patients’ clinical parameters and outcomes. Our results indicated that the BC cohort exhibited a higher mutation burden than the TCGA data. Mutations were identified in 46 out of 50 genes, including 21 novel mutations not previously reported in BC. The TP53 gene was mutated in 82.5% of the analyzed cohort, followed by PIK3 CA (45%), FGFR3 (43.75%) and APC (35%). TP53 mutations were associated with poor survival (p = 0.003) while the FGFR3 mutation group exhibited signs of good prognosis (p = 0.018). Bioinformatics highlighted significant gene interactions associated with poor prognosis. These findings underline the importance of identifying novel genetic mutations that could significantly improve prognostic stratification and expand therapeutic options for managing BC patients.https://doi.org/10.1038/s41598-025-04363-zBladder cancerGenesMutationPrognosisSequencing |
| spellingShingle | Taoufik Nedjadi Hifzur Ansari Muhammad A. Khan Naif Sannan Mubarak Al-Mansour Jaudah Al-Maghrabi Ashraf Dallol Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients Scientific Reports Bladder cancer Genes Mutation Prognosis Sequencing |
| title | Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| title_full | Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| title_fullStr | Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| title_full_unstemmed | Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| title_short | Clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| title_sort | clinical relevance of the somatic mutational landscaping in predicting outcome of bladder cancer patients |
| topic | Bladder cancer Genes Mutation Prognosis Sequencing |
| url | https://doi.org/10.1038/s41598-025-04363-z |
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