A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms
ObjectiveTo identify DNA methylation related biomarkers in patients with breast cancer (BC).Materials and MethodsA total of seven BC methylation studies including 1,438 BC patients or breast tissues were included in this study. An elastic net regularized Cox proportional hazards regression (CPH) mod...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmolb.2020.00118/full |
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| author | Xiao-Ping Liu Jinxuan Hou Chen Chen Chen Chen Li Guan Li Guan Han-Kun Hu Sheng Li Sheng Li |
| author_facet | Xiao-Ping Liu Jinxuan Hou Chen Chen Chen Chen Li Guan Li Guan Han-Kun Hu Sheng Li Sheng Li |
| author_sort | Xiao-Ping Liu |
| collection | DOAJ |
| description | ObjectiveTo identify DNA methylation related biomarkers in patients with breast cancer (BC).Materials and MethodsA total of seven BC methylation studies including 1,438 BC patients or breast tissues were included in this study. An elastic net regularized Cox proportional hazards regression (CPH) model was used to build a multi-5′-C-phosphate-G-3′ methylation panel. The diagnosis and prognosis power of the panel was evaluated and validated using a Kaplan–Meier curve, univariate and multivariable CPH, subgroup analysis. A nomogram containing the panel was developed. The relationships between the panel-based methylation risk and the immune landscape and genomic metrics were investigated.ResultsSixty-eight CpG sites were significantly correlated with the overall survival (OS) of BC patients, and based on the result of penalized CPH, a 28-CpG site based multi CpG methylation panel was found. The prognosis and diagnosis role of the panel was validated in the discovery set, validation set, and six independent cohorts, which indicated that higher methylation risk was associated with poor OS, and the panel outperformed currently available biomarkers and remained an independent factor after adjusting for other clinical features. The methylation risk was negatively correlated with innated and adaptive immune cells, and positively correlated with total mutation load, SCNA, and MATH.ConclusionsWe validated a multi CpG methylation panel that could independently predict the OS of BC patients. The Th2-mediated tumor promotion effect—suppression of innate and adaptive immunity—participated in the progression of high-risk BC. Patients with high methylation risk were associated with tumor heterogeneity and poor survival. |
| first_indexed | 2024-04-11T23:26:58Z |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-11T23:26:58Z |
| publishDate | 2020-07-01 |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-d3b662eaf1514a299c1d28166941bbc42022-12-22T03:57:17ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-07-01710.3389/fmolb.2020.00118539634A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its MechanismsXiao-Ping Liu0Jinxuan Hou1Chen Chen2Chen Chen3Li Guan4Li Guan5Han-Kun Hu6Sheng Li7Sheng Li8Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHuman Genetics Resource Preservation Center of Hubei Province, Wuhan, ChinaDepartment of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHuman Genetics Resource Preservation Center of Hubei Province, Wuhan, ChinaDepartment of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHuman Genetics Resource Preservation Center of Hubei Province, Wuhan, ChinaObjectiveTo identify DNA methylation related biomarkers in patients with breast cancer (BC).Materials and MethodsA total of seven BC methylation studies including 1,438 BC patients or breast tissues were included in this study. An elastic net regularized Cox proportional hazards regression (CPH) model was used to build a multi-5′-C-phosphate-G-3′ methylation panel. The diagnosis and prognosis power of the panel was evaluated and validated using a Kaplan–Meier curve, univariate and multivariable CPH, subgroup analysis. A nomogram containing the panel was developed. The relationships between the panel-based methylation risk and the immune landscape and genomic metrics were investigated.ResultsSixty-eight CpG sites were significantly correlated with the overall survival (OS) of BC patients, and based on the result of penalized CPH, a 28-CpG site based multi CpG methylation panel was found. The prognosis and diagnosis role of the panel was validated in the discovery set, validation set, and six independent cohorts, which indicated that higher methylation risk was associated with poor OS, and the panel outperformed currently available biomarkers and remained an independent factor after adjusting for other clinical features. The methylation risk was negatively correlated with innated and adaptive immune cells, and positively correlated with total mutation load, SCNA, and MATH.ConclusionsWe validated a multi CpG methylation panel that could independently predict the OS of BC patients. The Th2-mediated tumor promotion effect—suppression of innate and adaptive immunity—participated in the progression of high-risk BC. Patients with high methylation risk were associated with tumor heterogeneity and poor survival.https://www.frontiersin.org/article/10.3389/fmolb.2020.00118/fullbreast cancerDNA methylationprognosisdiagnosisimmune landscapegenomic metrics |
| spellingShingle | Xiao-Ping Liu Jinxuan Hou Chen Chen Chen Chen Li Guan Li Guan Han-Kun Hu Sheng Li Sheng Li A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms Frontiers in Molecular Biosciences breast cancer DNA methylation prognosis diagnosis immune landscape genomic metrics |
| title | A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms |
| title_full | A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms |
| title_fullStr | A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms |
| title_full_unstemmed | A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms |
| title_short | A DNA Methylation-Based Panel for the Prognosis and Dagnosis of Patients With Breast Cancer and Its Mechanisms |
| title_sort | dna methylation based panel for the prognosis and dagnosis of patients with breast cancer and its mechanisms |
| topic | breast cancer DNA methylation prognosis diagnosis immune landscape genomic metrics |
| url | https://www.frontiersin.org/article/10.3389/fmolb.2020.00118/full |
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