Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma
Open Access
- 12 April 2020
- journal article
- research article
- Published by Wiley in Liver International
- Vol. 40 (8), 1997-2007
- https://doi.org/10.1111/liv.14463
Abstract
Background & Aims Microvascular invasion (MVI) is a critical prognostic factor for operable hepatocellular carcinoma (HCC). This study aimed to explore the performance of circulating tumor DNA (ctDNA) in evaluating MVI status preoperatively. Methods Seventy‐three HCC patients were enrolled and randomly divided into a training cohort and a validation cohort in a 2:1 ratio, and preoperative blood and surgical tissue samples were obtained. Genomic alterations were analyzed using targeted deep sequencing with a 1021‐gene panel. Results In training cohort, 260 somatic mutations were identified in 40 blood samples (81.6%). CtDNA mutation was verified in paired tissue sample in 39 patients (97.5%). In univariate analysis, ctDNA allele frequency (AF) and largest tumor diameter were associated with the presence of MVI, but ctDNA AF was the only independent risk factor in multivariate analysis. With the cut‐off value of 0.83%, ctDNA AF determined the presence of MVI with the sensitivity of 89.7% and specificity of 80.0% in the training cohort, and the sensitivity of 78.6% and the specificity of 81.8% in the validation cohort. In preoperative evaluation, ctDNA AF, AFP level and BCLC staging were associated with recurrence‐free survival in both univariate and multivariate analysis. Conclusions CtDNA can serve as an independent risk factor of MVI for operable HCC and help determining precise treatment strategies. The integration of ctDNA in the management of operable HCC may achieve better clinical outcomes.Funding Information
- Chinese Foundation for Hepatitis Prevention and Control (TQGB20180120)
This publication has 37 references indexed in Scilit:
- Analysis of Circulating Tumor DNA to Monitor Metastatic Breast CancerThe New England Journal of Medicine, 2013
- Association between HBX status, aflatoxin-induced R249S TP53 mutation and risk of hepatocellular carcinoma in a case-control study from ThailandCancer Letters, 2012
- Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?Arab Journal of Gastroenterology, 2012
- miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinomaOncology Reports, 2012
- Gene-expression signature of vascular invasion in hepatocellular carcinomaJournal of Hepatology, 2011
- Seasonal Variation in TP53 R249S -Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus InfectionEnvironmental Health Perspectives, 2011
- Combining Clinical, Pathology, and Gene Expression Data to Predict Recurrence of Hepatocellular CarcinomaGastroenterology, 2011
- A System of Classifying Microvascular Invasion to Predict Outcome After Resection in Patients With Hepatocellular CarcinomaGastroenterology, 2009
- The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinomaMedical Oncology, 2009
- Risk of Recurrence in a Long-term Follow-up After Surgery in 417 Patients With Hepatitis B- or Hepatitis C-Related Hepatocellular CarcinomaAnnals of Surgery, 2006