Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population
Abstract Background The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their com...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-023-02900-6 |
| _version_ | 1827875568395223040 |
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| author | Kepu Zheng Leiyang Dai Yingpeng Zhao Laibang Li Wang Li Xibing Zhang Qiuming Su Ruichao Wu Yizhou Jiang Yonglin Chen Jianghua Ran |
| author_facet | Kepu Zheng Leiyang Dai Yingpeng Zhao Laibang Li Wang Li Xibing Zhang Qiuming Su Ruichao Wu Yizhou Jiang Yonglin Chen Jianghua Ran |
| author_sort | Kepu Zheng |
| collection | DOAJ |
| description | Abstract Background The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population. Methods A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3–4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients. Results At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89. Conclusions The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population. |
| first_indexed | 2024-03-12T17:08:47Z |
| format | Article |
| id | doaj.art-f6d3f284800e4d2aae5d479761212b88 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-03-12T17:08:47Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-f6d3f284800e4d2aae5d479761212b882023-08-06T11:16:12ZengBMCBMC Gastroenterology1471-230X2023-07-0123111410.1186/s12876-023-02900-6Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk populationKepu Zheng0Leiyang Dai1Yingpeng Zhao2Laibang Li3Wang Li4Xibing Zhang5Qiuming Su6Ruichao Wu7Yizhou Jiang8Yonglin Chen9Jianghua Ran10Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Clinical laboratory, Kunming Children’s HospitalDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of KunmingAbstract Background The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population. Methods A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3–4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients. Results At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89. Conclusions The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.https://doi.org/10.1186/s12876-023-02900-6SEPT9Septin9Hepatocellular carcinomaHCCScreeningHepatic cirrhosis |
| spellingShingle | Kepu Zheng Leiyang Dai Yingpeng Zhao Laibang Li Wang Li Xibing Zhang Qiuming Su Ruichao Wu Yizhou Jiang Yonglin Chen Jianghua Ran Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population BMC Gastroenterology SEPT9 Septin9 Hepatocellular carcinoma HCC Screening Hepatic cirrhosis |
| title | Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population |
| title_full | Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population |
| title_fullStr | Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population |
| title_full_unstemmed | Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population |
| title_short | Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population |
| title_sort | methylated sept9 combined with afp and pivka ii is effective for the detection of hcc in high risk population |
| topic | SEPT9 Septin9 Hepatocellular carcinoma HCC Screening Hepatic cirrhosis |
| url | https://doi.org/10.1186/s12876-023-02900-6 |
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