HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma
Abstract Background Early screening and detection of hepatocellular carcinoma (HCC) can efficiently improve patient prognosis. We aimed to identify a series of hypermethylated DNA markers and develop a blood-based HCC diagnosis panel containing DNA methylation sites and protein markers with improved...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-023-01508-7 |
| _version_ | 1797801398870474752 |
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| author | Yi Bai Juan Xu Deqiang Li Xiaoyu Zhang Dapeng Chen Fucun Xie Longmei Huang Xiaotian Yu Haitao Zhao Yamin Zhang |
| author_facet | Yi Bai Juan Xu Deqiang Li Xiaoyu Zhang Dapeng Chen Fucun Xie Longmei Huang Xiaotian Yu Haitao Zhao Yamin Zhang |
| author_sort | Yi Bai |
| collection | DOAJ |
| description | Abstract Background Early screening and detection of hepatocellular carcinoma (HCC) can efficiently improve patient prognosis. We aimed to identify a series of hypermethylated DNA markers and develop a blood-based HCC diagnosis panel containing DNA methylation sites and protein markers with improved sensitivity for early-stage HCC detection. Results Overall, 850K methylation arrays were performed using paired tissue DNA samples from 60 HCC patients. Ten candidate hypermethylated CpG sites were selected for further evaluation by quantitative methylation-specific PCR with 60 pairs of tissue samples. Six methylated CpG sites, along with α-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), were assayed in 150 plasma samples. Finally, an HCC diagnosis panel, named HepaClear, was developed in a cohort consisting of 296 plasma samples and validated in an independent cohort consisting of 198 plasma samples. The HepaClear panel, containing 3 hypermethylated CpG sites (cg14263942, cg12701184, and cg14570307) and 2 protein markers (AFP and DCP), yielded a sensitivity of 82.6% and a specificity of 96.2% in the training set and a sensitivity of 84.7% and a specificity of 92.0% in the validation set. The HepaClear panel had higher sensitivity (72.0%) for early-stage HCC than AFP (≥ 20 ng/mL, 48.0%) and DCP (≥ 40 mAU/mL, 62.0%) and detected 67.5% of AFP-negative HCC patients (AFP ≤ 20 ng/mL). Conclusions We developed a multimarker HCC detection panel (HepaClear) that shows high sensitivity for early-stage HCC. The HepaClear panel exhibits high potential for HCC screening and diagnosis from an at-risk population. |
| first_indexed | 2024-03-13T04:49:53Z |
| format | Article |
| id | doaj.art-d1b574fbf7d0468691fd7f41b39572b4 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-13T04:49:53Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-d1b574fbf7d0468691fd7f41b39572b42023-06-18T11:17:20ZengBMCClinical Epigenetics1868-70832023-06-0115111410.1186/s13148-023-01508-7HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinomaYi Bai0Juan Xu1Deqiang Li2Xiaoyu Zhang3Dapeng Chen4Fucun Xie5Longmei Huang6Xiaotian Yu7Haitao Zhao8Yamin Zhang9Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai UniversityDepartment of Infectious Diseases, Central Hospital of Shengli OilfieldHangzhou New Horizon Health Technology Co., LtdThe First Central Clinical School, Tianjin Medical UniversityThe First Central Clinical School, Tianjin Medical UniversityDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHangzhou New Horizon Health Technology Co., LtdHangzhou New Horizon Health Technology Co., LtdDepartment of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai UniversityAbstract Background Early screening and detection of hepatocellular carcinoma (HCC) can efficiently improve patient prognosis. We aimed to identify a series of hypermethylated DNA markers and develop a blood-based HCC diagnosis panel containing DNA methylation sites and protein markers with improved sensitivity for early-stage HCC detection. Results Overall, 850K methylation arrays were performed using paired tissue DNA samples from 60 HCC patients. Ten candidate hypermethylated CpG sites were selected for further evaluation by quantitative methylation-specific PCR with 60 pairs of tissue samples. Six methylated CpG sites, along with α-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), were assayed in 150 plasma samples. Finally, an HCC diagnosis panel, named HepaClear, was developed in a cohort consisting of 296 plasma samples and validated in an independent cohort consisting of 198 plasma samples. The HepaClear panel, containing 3 hypermethylated CpG sites (cg14263942, cg12701184, and cg14570307) and 2 protein markers (AFP and DCP), yielded a sensitivity of 82.6% and a specificity of 96.2% in the training set and a sensitivity of 84.7% and a specificity of 92.0% in the validation set. The HepaClear panel had higher sensitivity (72.0%) for early-stage HCC than AFP (≥ 20 ng/mL, 48.0%) and DCP (≥ 40 mAU/mL, 62.0%) and detected 67.5% of AFP-negative HCC patients (AFP ≤ 20 ng/mL). Conclusions We developed a multimarker HCC detection panel (HepaClear) that shows high sensitivity for early-stage HCC. The HepaClear panel exhibits high potential for HCC screening and diagnosis from an at-risk population.https://doi.org/10.1186/s13148-023-01508-7DNA methylationHepatocellular carcinoma850K methylation arrayMulti-target panelEarly detection |
| spellingShingle | Yi Bai Juan Xu Deqiang Li Xiaoyu Zhang Dapeng Chen Fucun Xie Longmei Huang Xiaotian Yu Haitao Zhao Yamin Zhang HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma Clinical Epigenetics DNA methylation Hepatocellular carcinoma 850K methylation array Multi-target panel Early detection |
| title | HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma |
| title_full | HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma |
| title_fullStr | HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma |
| title_full_unstemmed | HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma |
| title_short | HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma |
| title_sort | hepaclear a blood based panel combining novel methylated cpg sites and protein markers for the detection of early stage hepatocellular carcinoma |
| topic | DNA methylation Hepatocellular carcinoma 850K methylation array Multi-target panel Early detection |
| url | https://doi.org/10.1186/s13148-023-01508-7 |
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