IMM thesis: Promising biomarker for early diagnosis of liver cancer
Welcome to Shifeng Lian's presentation of his thesis ”Biomarkers for early detection and prognostic prediction of hepatocellular carcinoma”.
Time: October 15 at 9.00 AM
Location: Sal Petrén (Ground floor in Wargentinhuset), Nobels väg 12B
Supervisors: Zongli Zheng, Principal Investigator, Ming Wai Lau Centre for Reparative Medicine; and Fang Fang, Professor, Institute of Environmental Medicine (IMM)
Opponent: Florent Mouliere, Team leader, Cancer Research UK Manchester Institute, National Biomarker Centre
Three questions to Shifeng
What is the thesis about?
Circulating tumor DNA (ctDNA), which is shed from solid tumors into the bloodstream, offers a non-invasive method for detecting and monitoring cancer. This thesis aimed to identify effective ctDNA biomarkers for hepatocellular carcinoma (HCC) using blood samples collected both before and at the time of HCC diagnosis, focusing on biomarkers related to telomere and end sequences, genome-wide fragmentation, and copy number-based tumor content.
Can you tell us about some interesting results?
The most interesting result involved the telomere G-tail, which is a single-stranded DNA sequence located at the very ends of chromosomes and could not be captured by traditional double-stranded sequencing methods. Using our newly developed simple and direct BLESSING (bilateral single-strand sequencing) method, we observed that the short telomere G-tail was nearly 20 times more abundant in HCC patients than in HCC-free individuals. Based on this finding, we developed a model called telomere and end sequence in circulation (Telecon), which accurately separated HCC patients from HCC-free individuals. The performance of Telecon in detecting HCC was better when studying blood samples collected at the time of HCC diagnosis compared to blood samples collected longer time before diagnosis. While the analysis of DNA fragmentation patterns and tumor content also proved useful for detecting HCC and predicting patient outcomes, these methods were less effective than the Telecon method in identifying HCC patients using blood samples collected before diagnosis.
What further research is needed in the area?
This thesis provides valuable insights into the development of non-invasive circulating cell-free DNA (ccfDNA) biomarkers for early detection of HCC. The telomere G-tail could be a promising early detection biomarker for HCC. However, detecting HCC before clinical diagnosis remains challenging, and combining multiple biomarkers in future large-scale studies may help improve accuracy. Further research using new measurement technologies, such as efficient single-strand sequencing methods, will help provide a more detailed understanding of the biology of telomere G-tail shortening.