Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/10/1539 |
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| author | Yi-Chiao Cheng Po-Hsien Wu Yen-Ju Chen Cing-Han Yang Jhen-Li Huang Yu-Ching Chou Pi-Kai Chang Chia-Cheng Wen Shu-Wen Jao Hsin-Hui Huang Yi-Hsuan Tsai Tun-Wen Pai |
| author_facet | Yi-Chiao Cheng Po-Hsien Wu Yen-Ju Chen Cing-Han Yang Jhen-Li Huang Yu-Ching Chou Pi-Kai Chang Chia-Cheng Wen Shu-Wen Jao Hsin-Hui Huang Yi-Hsuan Tsai Tun-Wen Pai |
| author_sort | Yi-Chiao Cheng |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (<i>ADHFE1</i>, <i>SDC2</i>, and <i>PPP2R5C</i>) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated <i>ADHFE1</i>, <i>SDC2</i>, and <i>PPP2R5C</i> for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples. |
| first_indexed | 2024-03-10T06:33:11Z |
| format | Article |
| id | doaj.art-e29505e3423548b3835b4eda33f627d6 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T06:33:11Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e29505e3423548b3835b4eda33f627d62023-11-22T18:21:32ZengMDPI AGGenes2073-44252021-09-011210153910.3390/genes12101539Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA TestYi-Chiao Cheng0Po-Hsien Wu1Yen-Ju Chen2Cing-Han Yang3Jhen-Li Huang4Yu-Ching Chou5Pi-Kai Chang6Chia-Cheng Wen7Shu-Wen Jao8Hsin-Hui Huang9Yi-Hsuan Tsai10Tun-Wen Pai11Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, TaiwanDepartment of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, TaiwanDepartment of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, TaiwanSchool of Public Health, National Defense Medical Center, Taipei 11490, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, Taipei Medical University, Taipei 11042, TaiwanDepartment of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, TaiwanDepartment of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, TaiwanColorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (<i>ADHFE1</i>, <i>SDC2</i>, and <i>PPP2R5C</i>) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated <i>ADHFE1</i>, <i>SDC2</i>, and <i>PPP2R5C</i> for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.https://www.mdpi.com/2073-4425/12/10/1539DNA methylationelectronic medical recordsbiomarkerscolorectal cancerstool DNA test |
| spellingShingle | Yi-Chiao Cheng Po-Hsien Wu Yen-Ju Chen Cing-Han Yang Jhen-Li Huang Yu-Ching Chou Pi-Kai Chang Chia-Cheng Wen Shu-Wen Jao Hsin-Hui Huang Yi-Hsuan Tsai Tun-Wen Pai Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test Genes DNA methylation electronic medical records biomarkers colorectal cancer stool DNA test |
| title | Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test |
| title_full | Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test |
| title_fullStr | Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test |
| title_full_unstemmed | Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test |
| title_short | Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test |
| title_sort | using comorbidity pattern analysis to detect reliable methylated genes in colorectal cancer verified by stool dna test |
| topic | DNA methylation electronic medical records biomarkers colorectal cancer stool DNA test |
| url | https://www.mdpi.com/2073-4425/12/10/1539 |
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