Mutational signatures and their association with survival and gene expression in urological carcinomas
Different sources of mutagenesis cause consistently identifiable patterns of mutations and mutational signatures that mirror the various carcinogenetic processes. We used publicly available data from the Cancer Genome Atlas to evaluate the associations between the activity of the mutational signatur...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655862300057X |
| _version_ | 1797690955551211520 |
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| author | Peeter Karihtala Outi Kilpivaara Katja Porvari |
| author_facet | Peeter Karihtala Outi Kilpivaara Katja Porvari |
| author_sort | Peeter Karihtala |
| collection | DOAJ |
| description | Different sources of mutagenesis cause consistently identifiable patterns of mutations and mutational signatures that mirror the various carcinogenetic processes. We used publicly available data from the Cancer Genome Atlas to evaluate the associations between the activity of the mutational signatures and various survival endpoints in six types of urological cancers after adjusting for established prognostic factors. The predictive power of the signatures was evaluated with dynamic area under curve models. In addition, links between mutational signature activities and differences in gene expression patterns were analysed. APOBEC-related signature SBS2 was associated with improved overall survival (OS) and disease-specific survival (DSS) in bladder carcinomas in the multivariate analysis, while clock-like signature SBS1 predicted shortened DSS and progression-free interval (PFI) in clear cell renal cell carcinomas (ccRCC). In papillary renal cell carcinomas (pRCC), SBS45 was a predictor of improved outcomes, and APOBEC-related SBS13 was a predictor of worse outcomes. Gene expression analyses revealed various enriched pathways between the low- and high-signature groups. Interestingly, in both the ccRCC and pRCC cohorts, the genes of several members of the melanoma antigen (MAGE) family were highly upregulated in the signatures, which predicted poor outcomes, and downregulated in signatures, which were associated with improved survival. To summarize, SBS signatures provide substantial prognostic value compared with just the traditional prognostic factors in certain cancer types. APOBEC-related SBS2 and SBS13 seem to provide robust prognostic information for particular urological cancers, maybe driven by the expression of specific groups of genes, including the MAGE gene family. |
| first_indexed | 2024-03-12T02:06:34Z |
| format | Article |
| id | doaj.art-d01b28bbb0d94482abdf40baced304e6 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-03-12T02:06:34Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-d01b28bbb0d94482abdf40baced304e62023-09-07T04:43:21ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862023-10-0144100933Mutational signatures and their association with survival and gene expression in urological carcinomasPeeter Karihtala0Outi Kilpivaara1Katja Porvari2Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki FI-00290, Finland; Corresponding author.Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki FI-00014, Finland; Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; HUSLAB Laboratory of Genetics, HUS Diagnostic Center, Helsinki University Hospital, Helsinki FI-00014, FinlandDepartment of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu FI-90220, FinlandDifferent sources of mutagenesis cause consistently identifiable patterns of mutations and mutational signatures that mirror the various carcinogenetic processes. We used publicly available data from the Cancer Genome Atlas to evaluate the associations between the activity of the mutational signatures and various survival endpoints in six types of urological cancers after adjusting for established prognostic factors. The predictive power of the signatures was evaluated with dynamic area under curve models. In addition, links between mutational signature activities and differences in gene expression patterns were analysed. APOBEC-related signature SBS2 was associated with improved overall survival (OS) and disease-specific survival (DSS) in bladder carcinomas in the multivariate analysis, while clock-like signature SBS1 predicted shortened DSS and progression-free interval (PFI) in clear cell renal cell carcinomas (ccRCC). In papillary renal cell carcinomas (pRCC), SBS45 was a predictor of improved outcomes, and APOBEC-related SBS13 was a predictor of worse outcomes. Gene expression analyses revealed various enriched pathways between the low- and high-signature groups. Interestingly, in both the ccRCC and pRCC cohorts, the genes of several members of the melanoma antigen (MAGE) family were highly upregulated in the signatures, which predicted poor outcomes, and downregulated in signatures, which were associated with improved survival. To summarize, SBS signatures provide substantial prognostic value compared with just the traditional prognostic factors in certain cancer types. APOBEC-related SBS2 and SBS13 seem to provide robust prognostic information for particular urological cancers, maybe driven by the expression of specific groups of genes, including the MAGE gene family.http://www.sciencedirect.com/science/article/pii/S147655862300057XBladder carcinomaCOSMICMutationsRenal cell carcinoma cancerPrognosisSignature |
| spellingShingle | Peeter Karihtala Outi Kilpivaara Katja Porvari Mutational signatures and their association with survival and gene expression in urological carcinomas Neoplasia: An International Journal for Oncology Research Bladder carcinoma COSMIC Mutations Renal cell carcinoma cancer Prognosis Signature |
| title | Mutational signatures and their association with survival and gene expression in urological carcinomas |
| title_full | Mutational signatures and their association with survival and gene expression in urological carcinomas |
| title_fullStr | Mutational signatures and their association with survival and gene expression in urological carcinomas |
| title_full_unstemmed | Mutational signatures and their association with survival and gene expression in urological carcinomas |
| title_short | Mutational signatures and their association with survival and gene expression in urological carcinomas |
| title_sort | mutational signatures and their association with survival and gene expression in urological carcinomas |
| topic | Bladder carcinoma COSMIC Mutations Renal cell carcinoma cancer Prognosis Signature |
| url | http://www.sciencedirect.com/science/article/pii/S147655862300057X |
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