Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer
Abstract Non-small cell lung cancer (NSCLC) remains a formidable global health challenge, with heterogeneous molecular characteristics influencing prognosis and treatment response. We present a novel computational framework named ASTUTE (Association of SomaTic mUtaTions to gene Expression profiles),...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-01088-0 |
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| author | Valentina Crippa Nicoletta Cordani Alberto Maria Villa Federica Malighetti Matteo Villa Luca Sala Andrea Aroldi Rocco Piazza Diego Cortinovis Luca Mologni Daniele Ramazzotti |
| author_facet | Valentina Crippa Nicoletta Cordani Alberto Maria Villa Federica Malighetti Matteo Villa Luca Sala Andrea Aroldi Rocco Piazza Diego Cortinovis Luca Mologni Daniele Ramazzotti |
| author_sort | Valentina Crippa |
| collection | DOAJ |
| description | Abstract Non-small cell lung cancer (NSCLC) remains a formidable global health challenge, with heterogeneous molecular characteristics influencing prognosis and treatment response. We present a novel computational framework named ASTUTE (Association of SomaTic mUtaTions to gene Expression profiles), designed to perform genotype-phenotype mapping through the integration of genomic and transcriptomic data. Through the systematic analysis of over 3600 samples from diverse NSCLC datasets and multiple cancer types, we uncovered intricate associations between KEAP1/NFE2L2 mutations and the NRF2 pathway activation. Our study identified novel NRF2-related functionalities associated with specific genetic alterations and revealed a KEAP1/NFE2L2 expression signature predictive of prognosis across different cancer types. These findings enhance our understanding of cancer pathogenesis and drug resistance mechanisms mediated by NRF2 activation, paving the way for tailored therapeutic interventions and the development of prognostic biomarkers. Our approach exemplifies the power of integrating genomic and transcriptomic data to elucidate cancer mechanisms, thereby advancing the field of precision oncology. |
| format | Article |
| id | doaj-art-1c02d94602f342bcaf5eac02e7149079 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-1c02d94602f342bcaf5eac02e71490792025-08-24T11:05:50ZengNature Portfolionpj Precision Oncology2397-768X2025-08-019111210.1038/s41698-025-01088-0Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancerValentina Crippa0Nicoletta Cordani1Alberto Maria Villa2Federica Malighetti3Matteo Villa4Luca Sala5Andrea Aroldi6Rocco Piazza7Diego Cortinovis8Luca Mologni9Daniele Ramazzotti10Department of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaFondazione IRCCS San Gerardo dei Tintori di MonzaFondazione IRCCS San Gerardo dei Tintori di MonzaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaDepartment of Medicine and Surgery, University of Milano-BicoccaAbstract Non-small cell lung cancer (NSCLC) remains a formidable global health challenge, with heterogeneous molecular characteristics influencing prognosis and treatment response. We present a novel computational framework named ASTUTE (Association of SomaTic mUtaTions to gene Expression profiles), designed to perform genotype-phenotype mapping through the integration of genomic and transcriptomic data. Through the systematic analysis of over 3600 samples from diverse NSCLC datasets and multiple cancer types, we uncovered intricate associations between KEAP1/NFE2L2 mutations and the NRF2 pathway activation. Our study identified novel NRF2-related functionalities associated with specific genetic alterations and revealed a KEAP1/NFE2L2 expression signature predictive of prognosis across different cancer types. These findings enhance our understanding of cancer pathogenesis and drug resistance mechanisms mediated by NRF2 activation, paving the way for tailored therapeutic interventions and the development of prognostic biomarkers. Our approach exemplifies the power of integrating genomic and transcriptomic data to elucidate cancer mechanisms, thereby advancing the field of precision oncology.https://doi.org/10.1038/s41698-025-01088-0 |
| spellingShingle | Valentina Crippa Nicoletta Cordani Alberto Maria Villa Federica Malighetti Matteo Villa Luca Sala Andrea Aroldi Rocco Piazza Diego Cortinovis Luca Mologni Daniele Ramazzotti Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer npj Precision Oncology |
| title | Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer |
| title_full | Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer |
| title_fullStr | Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer |
| title_full_unstemmed | Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer |
| title_short | Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer |
| title_sort | integrative analysis of keap1 nfe2l2 alterations across 3600 tumors reveals an nrf2 expression signature as a prognostic biomarker in cancer |
| url | https://doi.org/10.1038/s41698-025-01088-0 |
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