Want to detect the development of pancreatic cancer and improve patient outcomes but don’t have any tissue biopsies? An exciting new epigenetics study that employed liquid biopsies to detect 5-hydroxymethylcytosine (5-hmC) on circulating cell-free DNA (cfDNA) to allow the early detection of pancreatic cancer now says: “No Problem!”
Researchers at Bluestar Genomics (San Diego, CA, USA), a startup from Steve Quake’s lab at Stanford University led by Dr. Samuel Levy, sought to explore the relationship between 5hmC in blood plasma-derived cfDNA in patients with pancreatic ductal adenocarcinoma (PDAC), a cancer that lacks robust diagnostic biomarkers for detection and treatment management. Here’s what their case-control study found:
- While the study encountered 5hmC enrichment at gene-centric functional regions and depletion at intergenic regions in both PDAC and non-cancer cfDNA, PDAC cfDNA displayed significant 5hmC gains and losses at genic regions compared to the non-cancer samples
- The group employed ChIP-Seq services from Active Motif to compare PDAC 5hmC profiles in tumor and cfDNA and tumor-derived chromatin states
- They found 5hmC enrichment at H3K4me3-marked active transcriptional start sites and enhancers along with weakly transcribed regions, where the most significant 5hmC changes in PDAC plasma occur, relative to cfDNA from control subjects
- This suggested that 5hmC associates with active transcription and proposed cfDNA 5hmC detection as a non-invasive means to monitor epigenomic dysregulation in tumors
- Interestingly, sites of differential PDAC cfDNA 5hmC occurred at genes related to pancreas development and cancer
- With this biologically significant data set, the study created a predictive model for the early detection of PDAC using the detection of cfDNA 5hmC levels that improved on predictions using a previously reported biomarker
Overall, this fascinating study highlights the analysis of cfDNA 5hmC from a liquid biopsy as a potentially effective means for early cancer detection that can improve patient outcomes. The authors anticipate that ongoing research into 5hmC levels on cfDNA will further improve PDAC detection and classification.
“Pancreatic cancer is a leading cause of cancer death globally and is often detected late when patients have few treatment options. While early detection is paramount to enable potentially curative treatments like surgery, there are currently no screening methods for it. This study demonstrates that our platform can identify pancreatic cancer at an early stage in a simple blood draw, which has significant potential to improve patient outcomes”, notes Gulfem Guler, Ph.D., lead author of the study.
Check out the diagnostic potential of 5hmC cfDNA profiles over at Nature Communications, October 2020.