Accession PRJCA001381
Title Comprehensive liquid profiling of circulating tumor DNA and protein biomarkers in long-term follow-up patients with hepatocellular carcinoma
Relevance Medical
Data types Whole genome sequencing
Exome
Targeted Locus (Loci)
Organisms Homo sapiens
Description Purpose: Circulating tumor DNA provides a novel approach for detecting tumor burden and predicting clinical outcomes of hepatocellular carcinoma. 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.Experimental design: 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.Results: 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.Conclusions: 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 2019-12-31
Publication
PubMed ID Article title Journal name DOI Year
31217202 Comprehensive Liquid Profiling of Circulating Tumor DNA and Protein Biomarkers in Long-Term Follow-Up Patients with Hepatocellular Carcinoma Clinical Cancer Research 10.1158/1078-0432.CCR-18-3477 2019
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) 2018ZX10302205
Submitter Xiaolong    Liu  (xiaoloong.liu@gmail.com)
Organization Mengchao Hepatobiliary Hospital of Fujian Medical University
Submission date 2019-04-18

Project Data

Resource name Description