Tumour DNA methylation markers associated with breast cancer survival: a replication study
Abstract Background Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies. Methods This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Au...
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BMC
2025-01-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-024-01955-x |
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| author | Elaheh Zarean Shuai Li Ee Ming Wong Enes Makalic Roger L. Milne Graham G. Giles Catriona McLean Melissa C. Southey Pierre-Antoine Dugué |
| author_facet | Elaheh Zarean Shuai Li Ee Ming Wong Enes Makalic Roger L. Milne Graham G. Giles Catriona McLean Melissa C. Southey Pierre-Antoine Dugué |
| author_sort | Elaheh Zarean |
| collection | DOAJ |
| description | Abstract Background Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies. Methods This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity). Cox proportional hazard regression analyses were conducted to assess associations between these markers and both breast cancer-specific survival and overall survival, adjusting for relevant participant characteristics. Results Our findings revealed partial replication for both individual CpG sites (9 out of 22) and multi-CpG signatures (2 out of 3). These associations were maintained after adjustment for participant characteristics and were stronger for breast cancer-specific mortality than for overall mortality. In fully-adjusted models, strong associations were observed for a CpG in PRAC2 (per standard deviation [SD], HR = 1.67, 95%CI: 1.24–2.25) and a signature based on 28 CpGs developed using elastic net (per SD, HR = 1.48, 95%CI: 1.09–2.00). Conclusions While further studies are needed to confirm and expand on these findings, our study suggests that DNA methylation markers hold promise for improving breast cancer prognostication. |
| format | Article |
| id | doaj-art-af12695091554bc1aaf956b54395e2e5 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-af12695091554bc1aaf956b54395e2e52025-01-19T12:44:09ZengBMCBreast Cancer Research1465-542X2025-01-012711810.1186/s13058-024-01955-xTumour DNA methylation markers associated with breast cancer survival: a replication studyElaheh Zarean0Shuai Li1Ee Ming Wong2Enes Makalic3Roger L. Milne4Graham G. Giles5Catriona McLean6Melissa C. Southey7Pierre-Antoine Dugué8Precision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityDepartment of Data Science and AI, Faculty of Information Technology, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityAnatomical Pathology, Alfred Health, The Alfred HospitalPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityAbstract Background Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies. Methods This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity). Cox proportional hazard regression analyses were conducted to assess associations between these markers and both breast cancer-specific survival and overall survival, adjusting for relevant participant characteristics. Results Our findings revealed partial replication for both individual CpG sites (9 out of 22) and multi-CpG signatures (2 out of 3). These associations were maintained after adjustment for participant characteristics and were stronger for breast cancer-specific mortality than for overall mortality. In fully-adjusted models, strong associations were observed for a CpG in PRAC2 (per standard deviation [SD], HR = 1.67, 95%CI: 1.24–2.25) and a signature based on 28 CpGs developed using elastic net (per SD, HR = 1.48, 95%CI: 1.09–2.00). Conclusions While further studies are needed to confirm and expand on these findings, our study suggests that DNA methylation markers hold promise for improving breast cancer prognostication.https://doi.org/10.1186/s13058-024-01955-xDNA methylationBreast cancerSurvivalFFPE tissuePrognostic factors |
| spellingShingle | Elaheh Zarean Shuai Li Ee Ming Wong Enes Makalic Roger L. Milne Graham G. Giles Catriona McLean Melissa C. Southey Pierre-Antoine Dugué Tumour DNA methylation markers associated with breast cancer survival: a replication study Breast Cancer Research DNA methylation Breast cancer Survival FFPE tissue Prognostic factors |
| title | Tumour DNA methylation markers associated with breast cancer survival: a replication study |
| title_full | Tumour DNA methylation markers associated with breast cancer survival: a replication study |
| title_fullStr | Tumour DNA methylation markers associated with breast cancer survival: a replication study |
| title_full_unstemmed | Tumour DNA methylation markers associated with breast cancer survival: a replication study |
| title_short | Tumour DNA methylation markers associated with breast cancer survival: a replication study |
| title_sort | tumour dna methylation markers associated with breast cancer survival a replication study |
| topic | DNA methylation Breast cancer Survival FFPE tissue Prognostic factors |
| url | https://doi.org/10.1186/s13058-024-01955-x |
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