A new biomarker panel accurately detected early stages of pancreatic ductal adenocarcinoma in human blood samples, according to new research.
The panel markers included the protein thrombospondin-2 (THBS2) combined with the known biomarker CA19-9, and could lead to earlier detection and better treatment for pancreatic cancer, the fourth leading cause of cancer-related deaths in the U.S., investigators said.
“Starting with our cell model that mimics human pancreatic cancer progression, we identified released proteins, then tested and validated a subset of these proteins as potential plasma biomarkers of this cancer,” Ken Zaret, PhD, director of the Penn Institute for Regenerative Medicine and the Joseph Leidy Professor of Cell and Developmental Biology, said in a press release.
Zaret and colleagues created a cell line from an advanced pancreatic ductal adenocarcinoma patient using stem cell technology, and genetically reprogrammed late-stage cancer cells to a stem cell state. This allowed them to make the reprogrammed cells revert to an early cancerous state, which revealed secreted blood biomarkers of early-stage disease.
Plasma THBS2 was the best candidate, so in multiple phases they used an enzyme-linked immunosorbent assay to screen for it in plasma samples from 746 patients with various stages of pancreatic ductal adenocarcinoma and benign pancreatic disease, and healthy controls.
They found that blood concentrations of THBS2 combined with CA19-9 reliably discriminated all stages of pancreatic ductal adenocarcinoma, with a specificity of 98% and a sensitivity of 87%. The panel also improved the ability to differentiate pancreatic cancer from pancreatitis.
“Positive results for THBS2 or CA19-9 concentrations in the blood consistently and correctly identified all stages of the cancer,” Zaret said in the press release. “Notably, THBS2 concentrations combined with CA19-9 identified early stages better than any other known method.”
The investigators now plan to validate the panel using samples collected from pancreatic cancer patients before they were diagnosed. Eventually, they expect it could be used in pancreatic cancer patients and individuals with a high risk for developing pancreatic cancer, such as first-degree relatives, those with a genetic predisposition, or people with a sudden onset of diabetes after age 50 years.
“Early detection of cancer has had a critical influence on lessening the impact of many types of cancer, including breast, colon, and cervical cancer,” Robert Vonderheide, MD, DPhil, director of the Abramson Cancer Center at the University of Pennsylvania, said in the press release. “A long-standing concern has been that patients with pancreatic cancer are often not diagnosed until it is too late for the best chance at effective treatment. Having a biomarker test for this disease could dramatically alter the outlook for these patients.” – by Adam Leitenberger
Disclosures: Zaret reports he has consulted for BetaLogics/Johnson & Johnson and RaNA Therapeutics, and along with another investigator, has a patent pending for the dual marker panel.