Urine DNA biomarkers for hepatocellular carcinoma screening

Amy K. Kim, James P. Hamilton, Selena Y. Lin, Ting Tsung Chang, Hie Won Hann, Chi Tan Hu, Yue Lou, Yih Jyh Lin, Terence P. Gade, Grace Park, Harry Luu, Tai Jung Lee, Jeremy Wang, Dion Chen, Michael G. Goggins, Surbhi Jain, Wei Song, Ying Hsiu Su

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Background: Hepatocellular carcinoma (HCC) occurs in a well-defined high-risk patient population, but better screening tests are needed to improve sensitivity and efficacy. Therefore, we investigated the use of urine circulating tumour DNA (ctDNA) as a screening test. Methods: Candidate markers in urine were selected from HCC and controls. We then enrolled 609 patients from five medical centres to test the selected urine panel. A two-stage model was developed to combine AFP and urine panel as a screening test. Results: Mutated TP53, and methylated RASSF1a, and GSTP1 were selected as the urine panel markers. Serum AFP outperformed the urine panel among all cases of HCC, but the urine panel identified 49% of HCC cases with low AFP < 20 ng/ml. Using the two-stage model, the combined AFP and urine panel identified 148 of the 186 HCC cases (79.6% sensitivity at 90% specificity), which was 30% more than the cases detected with serum AFP alone. It also increased early-stage HCC detection from 62% to 92% (BCLC stage 0), and 40% to 77% (BCLC stage A). Conclusion: Urine ctDNA has promising diagnostic utility in patients in HCC, especially in those with low AFP and can be used as a potential non-invasive HCC screening test.

Original languageEnglish
Pages (from-to)1432-1438
Number of pages7
JournalBritish Journal of Cancer
Volume126
Issue number10
DOIs
Publication statusPublished - 2022 Jun 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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