Accession |
PRJCA001358 |
Title |
Comprehensive liquid profiling of circulating tumor DNA and protein biomarkers in long-term follow-up patients with hepatocellular carcinoma |
Relevance |
Medical |
Data types |
Exome
Targeted Locus (Loci)
|
Organisms |
|
Description |
Purpose:Circulating tumor DNA (ctDNA) provides a novel approach for detecting tumor burden and predicting clinical outcomes of hepatocellular carcinoma (HCC). Here we performed a thorough evaluation of HCC circulating genetic features and further fully integrated them to build a robust strategy for HCC surveillance and prognostic outcome assessment. We performed target sequencing and low coverage whole genome sequencing on 168 plasma samples collected from 34 long-term follow-up HCC patients to capture tumor somatic SNVs and CNVs, respectively. Clinical information was also obtained to evaluate the prognostic performance of ctDNA comparing with clinically applied protein biomarkers.All plasma samples before surgery showed somatic genetic variations resembling corresponding tumor tissues.During follow up, SNVs and CNVs dynamically changed correlating to patients tumor burden.We integrated the comprehensive ctDNA mutation profiles to provide a robust strategy to accurately assess patients tumor burden with high consistence comparing to imaging results. This strategy could discover tumor occurrence in advance of imaging for an average of 4.6 months, and showed superior performance than serum biomarkers AFP, AFP-L3% and DCP. Furthermore, our strategy could precisely detect MRD in advance and predict patients prognostic outcomes for both RFS (p=0.001) and OS (p=0.001); further combining ctDNA with DCP could increase the sensitivity for MRD detection.We demonstrated that plasma CNV and SNV levels dynamically correlated with patients tumor burden in HCC. Our strategy of comprehensive mutation profile integration could accurately and better evaluate patients prognostic risk and detect tumor occurrence in advance than traditional strategies. |
Sample scope |
Multiisolate |
Release date |
2019-06-30 |
Grants |
Agency |
program |
Grant ID |
Grant title |
National Natural Science Foundation of China (NSFC)
|
Major Program
|
2018ZX10302205
|
|
|
Submitter |
Zhixiong
Cai (caizhixiong1985@163.com)
|
Organization |
Mengchao Hepatobiliary Hospital of Fujian Medical University |
Submission date |
2019-03-31 |