Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response
The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1375 |
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| author | Sheng-Chao Wang Li-Min Liao Muhamad Ansar Shih-Yun Lin Wei-Wen Hsu Chih-Ming Su Yu-Mei Chung Cai-Cing Liu Chin-Sheng Hung Ruo-Kai Lin |
| author_facet | Sheng-Chao Wang Li-Min Liao Muhamad Ansar Shih-Yun Lin Wei-Wen Hsu Chih-Ming Su Yu-Mei Chung Cai-Cing Liu Chin-Sheng Hung Ruo-Kai Lin |
| author_sort | Sheng-Chao Wang |
| collection | DOAJ |
| description | The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We analyzed a genome-wide methylation array in Taiwanese and The Cancer Genome Atlas (TCGA) breast cancer (BC) patients. Most breast cancer-specific circulating methylated <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> biomarkers were found in the plasma. An automatic analysis process of methylated ccfDNA was established. A combined analysis of <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> (CGIm) was performed in R using Recursive Partitioning and Regression Trees to establish a new prediction model. Combined analysis of <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> (CGIm) was found to have a sensitivity level of 97% and an area under the curve (AUC) of 0.955 in the training set, and a sensitivity level of 100% and an AUC of 0.961 in the test set. The circulating methylated <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> was also significantly decreased after surgery (all <i>p</i> < 0.001). The aberrant methylation patterns of the <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> genes means that they are potential biomarkers for the detection of early BC and can be combined with breast imaging data to achieve higher accuracy, sensitivity and specificity, facilitating breast cancer detection. They may also be applied to monitor the surgical treatment response. |
| first_indexed | 2024-03-10T13:07:40Z |
| format | Article |
| id | doaj.art-5b4d946a33954fe3b62268389c0fb94b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:07:40Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5b4d946a33954fe3b62268389c0fb94b2023-11-21T10:59:46ZengMDPI AGCancers2072-66942021-03-01136137510.3390/cancers13061375Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment ResponseSheng-Chao Wang0Li-Min Liao1Muhamad Ansar2Shih-Yun Lin3Wei-Wen Hsu4Chih-Ming Su5Yu-Mei Chung6Cai-Cing Liu7Chin-Sheng Hung8Ruo-Kai Lin9Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, No. 250, Wuxing Street, Taipei 110, TaiwanDivision of General Surgery, Department of Surgery, Taipei Medical University Shuang Ho Hospital, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, TaiwanPh.D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, TaiwanDepartment of Statistics, College of Arts and Sciences, Kansas State University, 101 Dickens Hall, 1116 Mid-Campus Drive N, Manhattan, KS 66506-0802, USADivision of General Surgery, Department of Surgery, Taipei Medical University Shuang Ho Hospital, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, TaiwanMaster Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, TaiwanSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, TaiwanDivision of General Surgery, Department of Surgery, Taipei Medical University Shuang Ho Hospital, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, TaiwanPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, No. 250, Wuxing Street, Taipei 110, TaiwanThe early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We analyzed a genome-wide methylation array in Taiwanese and The Cancer Genome Atlas (TCGA) breast cancer (BC) patients. Most breast cancer-specific circulating methylated <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> biomarkers were found in the plasma. An automatic analysis process of methylated ccfDNA was established. A combined analysis of <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> (CGIm) was performed in R using Recursive Partitioning and Regression Trees to establish a new prediction model. Combined analysis of <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> (CGIm) was found to have a sensitivity level of 97% and an area under the curve (AUC) of 0.955 in the training set, and a sensitivity level of 100% and an AUC of 0.961 in the test set. The circulating methylated <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> was also significantly decreased after surgery (all <i>p</i> < 0.001). The aberrant methylation patterns of the <i>CCDC181</i>, <i>GCM2</i> and <i>ITPRIPL1</i> genes means that they are potential biomarkers for the detection of early BC and can be combined with breast imaging data to achieve higher accuracy, sensitivity and specificity, facilitating breast cancer detection. They may also be applied to monitor the surgical treatment response.https://www.mdpi.com/2072-6694/13/6/1375breast cancerDNA methylationearly detectioncirculating cell-free DNAautomatic detectionsurgical treatment response |
| spellingShingle | Sheng-Chao Wang Li-Min Liao Muhamad Ansar Shih-Yun Lin Wei-Wen Hsu Chih-Ming Su Yu-Mei Chung Cai-Cing Liu Chin-Sheng Hung Ruo-Kai Lin Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response Cancers breast cancer DNA methylation early detection circulating cell-free DNA automatic detection surgical treatment response |
| title | Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response |
| title_full | Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response |
| title_fullStr | Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response |
| title_full_unstemmed | Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response |
| title_short | Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of <i>GCM2</i>, <i>ITPRIPL1</i> and <i>CCDC181</i> for Detection of Early Breast Cancer and Surgical Treatment Response |
| title_sort | automatic detection of the circulating cell free methylated dna pattern of i gcm2 i i itpripl1 i and i ccdc181 i for detection of early breast cancer and surgical treatment response |
| topic | breast cancer DNA methylation early detection circulating cell-free DNA automatic detection surgical treatment response |
| url | https://www.mdpi.com/2072-6694/13/6/1375 |
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