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Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation
| Content Provider | Scilit |
|---|---|
| Author | Kisiel, John B. Dukek, Brian A. Kanipakam, Reddappa V. S. R. Ghoz, Hassan M. Yab, Tracy C. Berger, Calise K. Taylor, William R. Foote, Patrick H. Giama, Nasra H. Onyirioha, Kristeen Abdallah, Mohamed A. Burger, Kelli N. Slettedahl, Seth Mahoney, Douglas W. Smyrk, Thomas C. Lewis, Jason T. Giakoumopoulos, Maria Allawi, Hatim T. Lidgard, Graham P. Roberts, Lewis R. Ahlquist, David A. |
| Copyright Year | 2019 |
| Description | Journal: Hepatology Early detection improves hepatocellular carcinoma (HCC) outcomes, but better noninvasive surveillance tools are needed. We aimed to identify and validate methylated DNA markers (MDMs) for HCC detection. Reduced representation bisulfite sequencing was performed on DNA extracted from 18 HCC and 35 control tissues. Candidate MDMs were confirmed by quantitative methylation specific PCR in DNA from independent tissues (74 HCC, 29 controls). A phase I plasma pilot incorporated quantitative allele‐specific real time target and signal amplification assays on independent plasma‐extracted DNA from 21 HCC cases and 30 cirrhotic controls. A phase II plasma study was then performed in 95 HCC cases, 51 cirrhosis controls, and 98 healthy controls using target enrichment long‐probe quantitative amplified signal (TELQAS) assays. Recursive partitioning identified best MDM combinations. The entire MDM panel was statistically cross‐validated by randomly splitting the data 2:1 for training and testing. Random forest regression models performed on the training set predicted disease status in the testing set; the median AUC (and 95% CI) were reported after 500 iterations. In phase II, a 6‐marker MDM panel (HOXA1, EMX1, AK055957, ECE1, PFKP and CLEC11A, normalized by B3GALT6 level yielded a best fit AUC of 0.96 (95% CI, 0.93‐0.99) with HCC sensitivity of 95% (88‐98%) at specificity of 92% (86‐96%). The panel detected 3/4 (75%) stage 0, 39/42 (93%) stage A, 13/14 (93%) stage B, 28/28 (100%) stage C and 7/7 (100%) stage D HCC. The AUC value for AFP was 0.80 (0.74‐0.87) compared to 0.94 (0.9‐0.97) for the cross‐validated MDM panel, P<0.0001. Conclusion Novel MDMs identified in this study proved to accurately detect HCC via plasma testing. Further optimization and clinical testing of this promising approach are indicated. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429916/pdf |
| Ending Page | 1192 |
| Page Count | 13 |
| Starting Page | 1180 |
| e-ISSN | 15273350 |
| DOI | 10.1002/hep.30244 |
| Journal | Hepatology |
| Issue Number | 3 |
| Volume Number | 69 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2019-02-05 |
| Access Restriction | Open |
| Subject Keyword | Journal: Hepatology Gastroenterology and Hepatology Early Detection of Cancer Liver Cirrhosis/complications Biomarkers/analysis |
| Content Type | Text |
| Resource Type | Article |
