Early Detection and Disease Monitoring of Hepatocellular Carcinoma Using Circulating Telomere DNA

Abstract

Early cancer detection requires high-performing biomarkers and effective tools to enable early intervention. Telomeres, located at the terminal of linear chromosomes, affect genome integrity and cell immortalization. At the very end of the telomere is a 3’ overhanging guanine-rich tail (G-tail) of which shortening is closely related to cell divisions. However, G-tail DNA cannot be detected with conventional sequencing technologies. Here we develop a high-preservation technology to quantify telomeres in circulating cell-free DNA and show that short G-tail DNA was nearly 20-fold higher in hepatocellular carcinoma patients with blood collected at diagnosis than controls and was also strongly correlated with poorer survival. We then used an independent prospective population cohort to show that the abundance of circulating short telomere G-tail increased with time approaching cancer diagnosis. These results indicate that circulating short-telomere G-tail, measured using our novel bilateral single-strand sequencing method, can effectively detect early and aggressive hepatocellular carcinoma.

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease

“…To the best of our knowledge, it is the first time to characterize the intimate relationship of TL and mtDNA-CN in patients with CVD. Specifically, higher levels of leu-TL and leu-mtDNA may indicate physiological condition or a compensation stage ( 11 ), while higher levels of cf-TL and cf-mtDNA may indicate pathological condition or a decompensation stage ( 50 , 53 ). Here, a mounting number of studies have been performed to provide evidence that TL and mtDNA are coordinately regulated ( 54 – 57 ).…”

“…It has been demonstrated that telomeres and mitochondria ( 79 ) from immune cells play critical roles in peripheral arterial disease ( 80 ) and heart failure ( 81 ), respectively. In contrast, while cf-TL and cf-mtDNA may indicate stages of decompensation ( 50 , 53 ). Therefore, both cf-TL and cf-mtDNA have been regarded as new biomarkers in cancer diagnosis and treatment ( 82 – 84 ).…”

Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies

“…As telomeric G-tail DNA cannot be detected with conventional sequencing technologies, Zheng et al developed a high-preservation technology to quantify telomeres in cfDNA. They showed that short G-tail DNA was nearly 20-fold higher in HCC patients than controls and was strongly correlated with lower survival [ 142 ]. A study by North indicated that serum cf-telDNA was present in glioblastoma patients at nearly double the amount of the levels in the non-cancer control group.…”