Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer
Summary: Background: Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). Methods: The OC-specific d...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Language: | English |
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Elsevier
2022-09-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422004042 |
| _version_ | 1811320939470651392 |
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| author | Leilei Liang Yu Zhang Chengcheng Li Yuchen Liao Guoqiang Wang Jiayue Xu Yifan Li Guangwen Yuan Yangchun Sun Rong Zhang Xiaoguang Li Weiqi Nian Jing Zhao Yuzi Zhang Xin Zhu Xiaofang Wen Shangli Cai Ning Li Lingying Wu |
| author_facet | Leilei Liang Yu Zhang Chengcheng Li Yuchen Liao Guoqiang Wang Jiayue Xu Yifan Li Guangwen Yuan Yangchun Sun Rong Zhang Xiaoguang Li Weiqi Nian Jing Zhao Yuzi Zhang Xin Zhu Xiaofang Wen Shangli Cai Ning Li Lingying Wu |
| author_sort | Leilei Liang |
| collection | DOAJ |
| description | Summary: Background: Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). Methods: The OC-specific differentially methylated regions (DMRs) were identified by sequencing ovarian tissue samples from OC (n = 61), benign ovarian disease (BOD, n = 49) and healthy controls (HC, n = 37). Based on 1,272 DMRs, a cfDNA OC detection model (OC-D model) was trained and validated in plasma samples from patients of OC (n = 104), BOD (n = 56) and HC (n = 56) and a prognostic testing model (OC-P model) was developed in plasma samples in patients with high-grade serous OC (HG-SOC) in the training cohort and then tested the rationality of this model with International Cancer Genome Consortium (ICGC) tissue methylation data. Mechanisms were investigated in the TCGA-OC cohort. Findings: In the validation cohort, the cfDNA OC-D model consisting of 18 DMRs achieved a sensitivity of 94.7% (95% CI: 85.4%‒98.9%) at a specificity of 88.7% (95% CI: 78.7%‒94.9%), which outperformed CA 125 (AUC: 0.967 vs 0.905, P = 0.03). Then the cfDNA OC-P model consisting of 15 DMRs was constructed and associated with a better prognosis of HG-SOC in multivariable Cox regression analysis (HR: 0.29, 95% CI, 0.11‒0.78, P = 0.01) in the training cohort, which was also observed in the ICGC cohort using tissue methylation (HR: 0.56, 95% CI, 0.32‒0.98, P = 0.04). Investigation into mechanisms revealed that the low-risk group had higher homologous recombination deficiency and immune cell infiltration (P < 0.05). Interpretation: Our study demonstrated the potential utility of cfDNA methylation in the detection and prognostic testing in OC. Future studies with a larger population are warranted. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector. |
| first_indexed | 2024-04-13T13:08:13Z |
| format | Article |
| id | doaj.art-3eee9305fcda4e7780bd5ed2fa77ac3b |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-13T13:08:13Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-3eee9305fcda4e7780bd5ed2fa77ac3b2022-12-22T02:45:42ZengElsevierEBioMedicine2352-39642022-09-0183104222Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancerLeilei Liang0Yu Zhang1Chengcheng Li2Yuchen Liao3Guoqiang Wang4Jiayue Xu5Yifan Li6Guangwen Yuan7Yangchun Sun8Rong Zhang9Xiaoguang Li10Weiqi Nian11Jing Zhao12Yuzi Zhang13Xin Zhu14Xiaofang Wen15Shangli Cai16Ning Li17Lingying Wu18Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Gynecology, Xiangya Hospital, Central South University, Changsha, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaChongqing University Cancer Hospital, Chongqing, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaBurning Rock Biotech, Guangdong, ChinaDepartment of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Corresponding authors at: Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, China.Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Corresponding authors at: Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, China.Summary: Background: Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). Methods: The OC-specific differentially methylated regions (DMRs) were identified by sequencing ovarian tissue samples from OC (n = 61), benign ovarian disease (BOD, n = 49) and healthy controls (HC, n = 37). Based on 1,272 DMRs, a cfDNA OC detection model (OC-D model) was trained and validated in plasma samples from patients of OC (n = 104), BOD (n = 56) and HC (n = 56) and a prognostic testing model (OC-P model) was developed in plasma samples in patients with high-grade serous OC (HG-SOC) in the training cohort and then tested the rationality of this model with International Cancer Genome Consortium (ICGC) tissue methylation data. Mechanisms were investigated in the TCGA-OC cohort. Findings: In the validation cohort, the cfDNA OC-D model consisting of 18 DMRs achieved a sensitivity of 94.7% (95% CI: 85.4%‒98.9%) at a specificity of 88.7% (95% CI: 78.7%‒94.9%), which outperformed CA 125 (AUC: 0.967 vs 0.905, P = 0.03). Then the cfDNA OC-P model consisting of 15 DMRs was constructed and associated with a better prognosis of HG-SOC in multivariable Cox regression analysis (HR: 0.29, 95% CI, 0.11‒0.78, P = 0.01) in the training cohort, which was also observed in the ICGC cohort using tissue methylation (HR: 0.56, 95% CI, 0.32‒0.98, P = 0.04). Investigation into mechanisms revealed that the low-risk group had higher homologous recombination deficiency and immune cell infiltration (P < 0.05). Interpretation: Our study demonstrated the potential utility of cfDNA methylation in the detection and prognostic testing in OC. Future studies with a larger population are warranted. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.http://www.sciencedirect.com/science/article/pii/S2352396422004042Ovarian cancerMethylationCirculating cell-free DNAOvarian cancer detectionPrognosisLiquid biopsy |
| spellingShingle | Leilei Liang Yu Zhang Chengcheng Li Yuchen Liao Guoqiang Wang Jiayue Xu Yifan Li Guangwen Yuan Yangchun Sun Rong Zhang Xiaoguang Li Weiqi Nian Jing Zhao Yuzi Zhang Xin Zhu Xiaofang Wen Shangli Cai Ning Li Lingying Wu Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer EBioMedicine Ovarian cancer Methylation Circulating cell-free DNA Ovarian cancer detection Prognosis Liquid biopsy |
| title | Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer |
| title_full | Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer |
| title_fullStr | Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer |
| title_full_unstemmed | Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer |
| title_short | Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer |
| title_sort | plasma cfdna methylation markers for the detection and prognosis of ovarian cancer |
| topic | Ovarian cancer Methylation Circulating cell-free DNA Ovarian cancer detection Prognosis Liquid biopsy |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422004042 |
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