New protein markers distinguish cancer from non-cancer and track treatment responses
Two proteins contained within cellular “bubbles” cast off from cancer cells can be used as biomarkers to accurately detect pancreatic ductal adenocarcinoma (PDAC), according to a new study by led by researchers from Translational Genomics Research Institute (TGen), part of City of Hope.
The scientists measured concentrations of exosomes containing ALPPL2 and THBS2, two proteins associated with PDAC, in 219 blood samples, including patients with early and late-stage PDAC, non-cancerous pancreatic diseases, and healthy individuals. Exosomal ALPP2 and THBS2 measurements can distinguish PDAC cases from non-cancer cases with high specificity and sensitivity, the researchers concluded.
In a second group of 26 patients undergoing treatment for advanced PDAC, the exosomal proteins were also used as reliable biomarkers for tracking the progress of PDAC treatment, decreasing in concentration as tumors shrank, the researchers report in the British Journal of Cancer.
The findings could provide a much-needed new biomarker for PDAC, a cancer that has very few options for early detection and monitoring. Although PDAC is the most common type of pancreatic cancer, it is mostly diagnosed in its late stages, when only 15-20% of patients can be treated with the surgery that offers the best chance for long-term survival.
PDAC is detected now mostly through imaging such as CT scans and MRI, or through elevated levels of Carbohydrate Antigen 19-9 (CA19-9), said Haiyong Han, Ph.D., a professor in the Clinical Genomics and Therapeutics Division at TGen and senior author of the study.
“CA19-9 is primarily used to monitor disease rather than for early detection, since its sensitivity and specificity are not high enough for effective screening,” Han explained. “In fact, nearly 20% of pancreatic cancer patients never show elevated CA19-9 levels.”
In their search for a better PDAC biomarker, Han and colleagues turned to exosomes. Exosomes are tiny bubbles formed within a cell through its recycling system (called endosomes). They are later released into the space around the cell and some eventually enter the blood circulation. These vesicles can contain pieces of RNA, DNA, proteins or other material from the original cell.
Exosomes formed by cancer cells “may contain molecules that are specific to that cancer cell and are absent or present at very low levels in normal cells, which makes them a good place to look for cancer biomarkers,” said Han.
The researchers measured the concentration of exosomes with proteins potentially specific to PDAC in patient samples said Kuntal Halder, PhD, a TGen staff scientist and first author of the study.
“We looked for the PDAC-related protein biomarkers in and outside of exosomes across all samples,” said Halder, “Be we found that the markers showed higher sensitivity and specificity when measured in blood exosomes compared to measuring their total levels in the blood.”
The research team is planning new studies to use the biomarkers in different types of patient groups.
“One, we are trying to see if we can use our markers to detect high-grade dysplasia or invasive cancer in patients with pancreatic cysts,” Han said.
If clinicians had more information about whether a patient’s benign cysts might be progressing toward cancer, it could help with decisions about whether and when to have surgery for the cysts.
“Having a biomarker that can tell physicians the difference between benign disease and cancer can lead to significant improvement in survival for individuals with pancreatic cysts and pancreatic cancer. We are excited about the results of this collaborative research with Dr. Han and team,” said, Erkut Borazanci, M.D., medical director of the Oncology Research Division at HonorHealth Research Institute and a study author.
According to Han, a follow-on study, will look at PDAC patients with non-elevated CA19-9 to see if the markers can be used to monitor their disease with greater frequency and less cost, for example, allowing for testing every two weeks rather than every two months through imaging.
The Flinn Foundation, the Dorrance Family Fund, the Marley Foundation, the Seena Magowitz Foundation, Purple Pansies, John E. Sabga Foundation, the TGen Pancreatic Cancer National Advisory Council, HonorHealth Foundation, and NIH/NCI (U01CA214254) funded this research.
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By: Becky Ham | September 3, 2025 | Original Post