Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival
The increasing prevalence of diagnosed breast cancer cases emphasizes the urgent demand for developing new prognostic breast cancer biomarkers. Copy number alteration (CNA) burden measured as the percentage of the genome affected by CNAs has emerged as a potential candidate to this aim. Using somati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00421/full |
| _version_ | 1828276688119660544 |
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| author | Linfan Zhang Linfan Zhang Nikta Feizi Nikta Feizi Chen Chi Chen Chi Pingzhao Hu Pingzhao Hu Pingzhao Hu Pingzhao Hu |
| author_facet | Linfan Zhang Linfan Zhang Nikta Feizi Nikta Feizi Chen Chi Chen Chi Pingzhao Hu Pingzhao Hu Pingzhao Hu Pingzhao Hu |
| author_sort | Linfan Zhang |
| collection | DOAJ |
| description | The increasing prevalence of diagnosed breast cancer cases emphasizes the urgent demand for developing new prognostic breast cancer biomarkers. Copy number alteration (CNA) burden measured as the percentage of the genome affected by CNAs has emerged as a potential candidate to this aim. Using somatic CNA data obtained from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), we implemented Kaplan-Meier estimators and Cox proportional hazards models to examine the association of CNA burden with patient’s overall survival (OS) and disease specific survival (DSS). We also evaluated the association by considering patients’ age and tumor subtypes using stratified Cox models. We delineated the distribution of CNA burden in sample genomes and highlighted chromosomes 1, 8, and 16 as the carriers of the highest CNA burden. We identified a strong association between CNA burden and age as well as CNA burden and breast cancer PAM50 subtypes. We found that controlling the effects of both age (bound by 45-year) and PAM50 subtypes on patient survival using stratified Cox models, would still result in significant association between CNA burden and patients overall survival in both Discovery and Validation data. The same trend was observed in disease specific survival when only PAM50 subtypes were controlled in the stratified Cox models. Our analysis showed that there is a significant association between CNA burden and breast cancer survival. This result is also validated by using TCGA (The Cancer Genome Atlas) data. CNA burden of breast cancer patients has a considerable potential to be used as a novel prognostic biomarker. |
| first_indexed | 2024-04-13T07:01:13Z |
| format | Article |
| id | doaj.art-9e36375e32994adfa3edbc48656449dd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T07:01:13Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-9e36375e32994adfa3edbc48656449dd2022-12-22T02:57:07ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-10-01910.3389/fgene.2018.00421409435Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer SurvivalLinfan Zhang0Linfan Zhang1Nikta Feizi2Nikta Feizi3Chen Chi4Chen Chi5Pingzhao Hu6Pingzhao Hu7Pingzhao Hu8Pingzhao Hu9Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, CanadaCentre for Healthcare Innovation, Winnipeg Regional Health Authority and University of Manitoba, Winnipeg, MB, CanadaDepartment of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, CanadaCentre for Healthcare Innovation, Winnipeg Regional Health Authority and University of Manitoba, Winnipeg, MB, CanadaDepartment of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, CanadaCentre for Healthcare Innovation, Winnipeg Regional Health Authority and University of Manitoba, Winnipeg, MB, CanadaDepartment of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, CanadaCentre for Healthcare Innovation, Winnipeg Regional Health Authority and University of Manitoba, Winnipeg, MB, CanadaDepartment of Electrical and Computer Engineering, University of Manitoba, Winnipeg, MB, CanadaDepartment of Computer Science, University of Manitoba, Winnipeg, MB, CanadaThe increasing prevalence of diagnosed breast cancer cases emphasizes the urgent demand for developing new prognostic breast cancer biomarkers. Copy number alteration (CNA) burden measured as the percentage of the genome affected by CNAs has emerged as a potential candidate to this aim. Using somatic CNA data obtained from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), we implemented Kaplan-Meier estimators and Cox proportional hazards models to examine the association of CNA burden with patient’s overall survival (OS) and disease specific survival (DSS). We also evaluated the association by considering patients’ age and tumor subtypes using stratified Cox models. We delineated the distribution of CNA burden in sample genomes and highlighted chromosomes 1, 8, and 16 as the carriers of the highest CNA burden. We identified a strong association between CNA burden and age as well as CNA burden and breast cancer PAM50 subtypes. We found that controlling the effects of both age (bound by 45-year) and PAM50 subtypes on patient survival using stratified Cox models, would still result in significant association between CNA burden and patients overall survival in both Discovery and Validation data. The same trend was observed in disease specific survival when only PAM50 subtypes were controlled in the stratified Cox models. Our analysis showed that there is a significant association between CNA burden and breast cancer survival. This result is also validated by using TCGA (The Cancer Genome Atlas) data. CNA burden of breast cancer patients has a considerable potential to be used as a novel prognostic biomarker.https://www.frontiersin.org/article/10.3389/fgene.2018.00421/fullcopy number alterationgenetic burdenprognosis biomarkerbreast cancerstratified model |
| spellingShingle | Linfan Zhang Linfan Zhang Nikta Feizi Nikta Feizi Chen Chi Chen Chi Pingzhao Hu Pingzhao Hu Pingzhao Hu Pingzhao Hu Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival Frontiers in Genetics copy number alteration genetic burden prognosis biomarker breast cancer stratified model |
| title | Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival |
| title_full | Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival |
| title_fullStr | Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival |
| title_full_unstemmed | Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival |
| title_short | Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival |
| title_sort | association analysis of somatic copy number alteration burden with breast cancer survival |
| topic | copy number alteration genetic burden prognosis biomarker breast cancer stratified model |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00421/full |
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