Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons
IntroductionMetastatic colorectal cancer (mCRC) is a disease with various molecular profiles that exhibit different evolution patterns. Although most mCRC patients receive the same chemotherapy drugs in the first-line setting, treatment response is heterogeneous suggesting some tumors are inherently...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1557609/full |
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| author | Vlad Adrian Afrăsânie Vlad Adrian Afrăsânie Mihai Vasile Marinca Mihai Vasile Marinca Bogdan Gafton Bogdan Gafton Alexandra Rusu Eliza Maria Froicu Eliza Maria Froicu Daniel Sur Daniel Sur Cristian Virgil Lungulescu Raluca Cezara Popa Irina Afrăsânie Anca Viorica Ivanov Georgiana Emmanuela Gîlcă-Blanariu Lucian Miron Lucian Miron Cristina Rusu Teodora Alexa-Stratulat Teodora Alexa-Stratulat |
| author_facet | Vlad Adrian Afrăsânie Vlad Adrian Afrăsânie Mihai Vasile Marinca Mihai Vasile Marinca Bogdan Gafton Bogdan Gafton Alexandra Rusu Eliza Maria Froicu Eliza Maria Froicu Daniel Sur Daniel Sur Cristian Virgil Lungulescu Raluca Cezara Popa Irina Afrăsânie Anca Viorica Ivanov Georgiana Emmanuela Gîlcă-Blanariu Lucian Miron Lucian Miron Cristina Rusu Teodora Alexa-Stratulat Teodora Alexa-Stratulat |
| author_sort | Vlad Adrian Afrăsânie |
| collection | DOAJ |
| description | IntroductionMetastatic colorectal cancer (mCRC) is a disease with various molecular profiles that exhibit different evolution patterns. Although most mCRC patients receive the same chemotherapy drugs in the first-line setting, treatment response is heterogeneous suggesting some tumors are inherently resistant to oxaliplatin/fluoropyrimidine regimen. Genomic-based markers may help identify these patients and guidetreatment decisions due to potential prognostic and predictive value.MethodsWe performed a retrospective analysis on 77 patients diagnosed with mCRC treated with an oxaliplatin/fluoropyrimidine regimen in the Regional Institute of Oncology Iaşi between April 2017 and December 2019. We studied the impact of KRAS, NRAS, BRAF, PIK3CA and TP53 genes and their mutations in a treatment-naive population.ResultsThe median progression free survival (PFS) was 11 months (95% CI, 10.2-11.7 months) and the median overall survival (OS) was 23.6 months (16.3-30.8 months). Multivariate analysis of factors affecting PFS revealed that KRAS exon –3 mutation was associated with quicker progression while on oxaliplatin-based chemotherapy. A similar analysis indicated that the KRAS exon –3 mutation was also associated with decreased OS (p=0.03). The presence of the TP53 in exon 8 was associated with an increased OS (p=0.001).DiscussionThe present analysis offers insights into the prognostic implications of genes and exon-distributed mutations within RAS, BRAF, PIK3CA, and TP53 in mCRC. Subsequent prospective investigations with a more extensive patient cohort are needed to clarify the influence of exon-distributed mutations on therapeutic decision-making and prognostic outcomes. |
| format | Article |
| id | doaj-art-5e6c8027e747488cbb6552e879889655 |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-5e6c8027e747488cbb6552e8798896552025-08-20T02:33:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15576091557609Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exonsVlad Adrian Afrăsânie0Vlad Adrian Afrăsânie1Mihai Vasile Marinca2Mihai Vasile Marinca3Bogdan Gafton4Bogdan Gafton5Alexandra Rusu6Eliza Maria Froicu7Eliza Maria Froicu8Daniel Sur9Daniel Sur10Cristian Virgil Lungulescu11Raluca Cezara Popa12Irina Afrăsânie13Anca Viorica Ivanov14Georgiana Emmanuela Gîlcă-Blanariu15Lucian Miron16Lucian Miron17Cristina Rusu18Teodora Alexa-Stratulat19Teodora Alexa-Stratulat20Department of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Medical Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, Cluj-Napoca, RomaniaDepartment of Oncology, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Pediatrics, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Gastroenterology, University of Medicine and Pharmacy “Grigore T. Popa”, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Genetics, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaDepartment of Medical Oncology, Regional Institute of Oncology, Iasi, RomaniaDepartment of Medical Oncology-Radiation Therapy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, RomaniaIntroductionMetastatic colorectal cancer (mCRC) is a disease with various molecular profiles that exhibit different evolution patterns. Although most mCRC patients receive the same chemotherapy drugs in the first-line setting, treatment response is heterogeneous suggesting some tumors are inherently resistant to oxaliplatin/fluoropyrimidine regimen. Genomic-based markers may help identify these patients and guidetreatment decisions due to potential prognostic and predictive value.MethodsWe performed a retrospective analysis on 77 patients diagnosed with mCRC treated with an oxaliplatin/fluoropyrimidine regimen in the Regional Institute of Oncology Iaşi between April 2017 and December 2019. We studied the impact of KRAS, NRAS, BRAF, PIK3CA and TP53 genes and their mutations in a treatment-naive population.ResultsThe median progression free survival (PFS) was 11 months (95% CI, 10.2-11.7 months) and the median overall survival (OS) was 23.6 months (16.3-30.8 months). Multivariate analysis of factors affecting PFS revealed that KRAS exon –3 mutation was associated with quicker progression while on oxaliplatin-based chemotherapy. A similar analysis indicated that the KRAS exon –3 mutation was also associated with decreased OS (p=0.03). The presence of the TP53 in exon 8 was associated with an increased OS (p=0.001).DiscussionThe present analysis offers insights into the prognostic implications of genes and exon-distributed mutations within RAS, BRAF, PIK3CA, and TP53 in mCRC. Subsequent prospective investigations with a more extensive patient cohort are needed to clarify the influence of exon-distributed mutations on therapeutic decision-making and prognostic outcomes.https://www.frontiersin.org/articles/10.3389/fonc.2025.1557609/fullmetastatic colorectal cancerpredictive biomarkersprognostic biomarkersKRASNRASBRAF |
| spellingShingle | Vlad Adrian Afrăsânie Vlad Adrian Afrăsânie Mihai Vasile Marinca Mihai Vasile Marinca Bogdan Gafton Bogdan Gafton Alexandra Rusu Eliza Maria Froicu Eliza Maria Froicu Daniel Sur Daniel Sur Cristian Virgil Lungulescu Raluca Cezara Popa Irina Afrăsânie Anca Viorica Ivanov Georgiana Emmanuela Gîlcă-Blanariu Lucian Miron Lucian Miron Cristina Rusu Teodora Alexa-Stratulat Teodora Alexa-Stratulat Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons Frontiers in Oncology metastatic colorectal cancer predictive biomarkers prognostic biomarkers KRAS NRAS BRAF |
| title | Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons |
| title_full | Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons |
| title_fullStr | Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons |
| title_full_unstemmed | Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons |
| title_short | Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by exons |
| title_sort | navigating beyond the surface prognostic significance of kras nras braf pik3ca and tp53 mutations examined by exons |
| topic | metastatic colorectal cancer predictive biomarkers prognostic biomarkers KRAS NRAS BRAF |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1557609/full |
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