Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers
Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DN...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/11/1/51 |
| _version_ | 1797542875051851776 |
|---|---|
| author | Nam-Yun Cho Ji-Won Park Xianyu Wen Yun-Joo Shin Jun-Kyu Kang Sang-Hyun Song Hwang-Phill Kim Tae-You Kim Jeong Mo Bae Gyeong Hoon Kang |
| author_facet | Nam-Yun Cho Ji-Won Park Xianyu Wen Yun-Joo Shin Jun-Kyu Kang Sang-Hyun Song Hwang-Phill Kim Tae-You Kim Jeong Mo Bae Gyeong Hoon Kang |
| author_sort | Nam-Yun Cho |
| collection | DOAJ |
| description | Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (<i>ADGRB1</i>, <i>ANKRD13</i>, <i>FAM123A</i>, <i>GLI3</i>, <i>PCDHG</i>, <i>PPP1R16B</i>, <i>SLIT3</i>, and <i>TMEM90B</i>) and developed a five-marker panel (<i>FAM123A</i>, <i>GLI3</i>, <i>PPP1R16B</i>, <i>SLIT3</i>, and <i>TMEM90B</i>) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (<i>n</i> = 117) and healthy volunteers (<i>n</i> = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC. |
| first_indexed | 2024-03-10T13:36:41Z |
| format | Article |
| id | doaj.art-4f8d0b829bb8434cb460d253f787f7c1 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T13:36:41Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-4f8d0b829bb8434cb460d253f787f7c12023-11-21T07:27:37ZengMDPI AGDiagnostics2075-44182020-12-011115110.3390/diagnostics11010051Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation MarkersNam-Yun Cho0Ji-Won Park1Xianyu Wen2Yun-Joo Shin3Jun-Kyu Kang4Sang-Hyun Song5Hwang-Phill Kim6Tae-You Kim7Jeong Mo Bae8Gyeong Hoon Kang9Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of General Surgery, Seoul National University College of Medicine, Seoul 03030, KoreaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, KoreaLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, KoreaCancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (<i>ADGRB1</i>, <i>ANKRD13</i>, <i>FAM123A</i>, <i>GLI3</i>, <i>PCDHG</i>, <i>PPP1R16B</i>, <i>SLIT3</i>, and <i>TMEM90B</i>) and developed a five-marker panel (<i>FAM123A</i>, <i>GLI3</i>, <i>PPP1R16B</i>, <i>SLIT3</i>, and <i>TMEM90B</i>) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (<i>n</i> = 117) and healthy volunteers (<i>n</i> = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.https://www.mdpi.com/2075-4418/11/1/51cfDNAcolorectal cancerdroplet digital PCRMethyLightmethylationplasma |
| spellingShingle | Nam-Yun Cho Ji-Won Park Xianyu Wen Yun-Joo Shin Jun-Kyu Kang Sang-Hyun Song Hwang-Phill Kim Tae-You Kim Jeong Mo Bae Gyeong Hoon Kang Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers Diagnostics cfDNA colorectal cancer droplet digital PCR MethyLight methylation plasma |
| title | Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers |
| title_full | Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers |
| title_fullStr | Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers |
| title_full_unstemmed | Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers |
| title_short | Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers |
| title_sort | blood based detection of colorectal cancer using cancer specific dna methylation markers |
| topic | cfDNA colorectal cancer droplet digital PCR MethyLight methylation plasma |
| url | https://www.mdpi.com/2075-4418/11/1/51 |
| work_keys_str_mv | AT namyuncho bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT jiwonpark bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT xianyuwen bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT yunjooshin bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT junkyukang bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT sanghyunsong bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT hwangphillkim bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT taeyoukim bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT jeongmobae bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers AT gyeonghoonkang bloodbaseddetectionofcolorectalcancerusingcancerspecificdnamethylationmarkers |