A Novel Extracellular Vesicle Protein-based Blood Test Identifies 95% of Stage 1 Pancreatic Cancer

Finding cancer at early stages significantly increases patient survival rates, however,  early detection can be difficult in a number of solid tumors. For example, pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers and a leading cause of all cancer-related deaths in the United States, typically goes undetected until it progresses to advanced, metastatic disease, when surgical resection is no longer curative. Hence, the ability to start treating the disease while it is still localized is a major factor for improving 5-year survival rates. [1][2]

A new screening platform, called high-conductance di-electrophoresis, which was developed at Moores Cancer Center at UC San Diego Health 12 years ago, may change this. In one pilot study, researchers using the technology, flagged more than 95% of stage 1 pancreatic cancers.  The results of the study were published in Nature Communications Medicine.[3]

If validated by future studies, this approach may offer a new way to detect the third-leading cause of U.S. cancer deaths in 2020.

Funded, in part, by the National Institutes of Health and the Stand Up To Cancer–Lustgarten Foundation, this study was the first clinical test of a novel platform technology.

Conducted by a team of researchers from the Translational Genomics Research Institute (TGen) and City of Hope National Medical Center, in collaboration with the University of Texas MD Anderson Cancer Center, the San Diego Cancer Research Institute and Biological Dynamics, the researchers, using the new technology, were able to detects tell-tale proteins released into circulation by cancer cells.

Extracellular vesicles
The technology is designed to detects these tell-tale tumor proteins known as extracellular vesicles (EVs), that are released into circulation by cancer cells as part of a poorly understood intercellular communication network.

Using an alternating current electrokinetics (ACE) platform technology to purifies extracellular vesicles from plasma, the researchers, in a next step, used an Artificial intelligence (AI) -enabled multi-marker EV-protein measurements to develop a machine learning algorithm that can discriminate cancer cases from controls to predict the likelihood of malignancy.

In the case-control pilot study, the researchers compared 139 pathologically confirmed stage I and II cancer cases from patients diagnosed with pancreatic, ovarian, or bladder cancer, against 184 controls.  The results demonstrated an area under the curve (AUC) of 0.95 (95% CI: 0.92 to 0.97), with sensitivity of 71.2% (95% CI: 63.2 to 78.1) at 99.5% (97.0 to 99.9) specificity.

The researchers noted that the sensitivity was similar at both early stages [stage I: 70.5% (60.2 to 79.0) and stage II: 72.5% (59.1 to 82.9)]. Detection of stage I cancer reached 95.5% in stage 1 pancreatic cancers, 74.4% in ovarian, including stage 1 ovarian cancer and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas — all with more than 99% specificity, and 43.8% in bladder cancer.

Particular promising
These results are clearly illustrating the potential value of this technology for early cancer detection.

“The pancreatic cancer result is particular promising,” said Scott M. Lippman, MD, director of Moores Cancer Center, principal Investigator of the Stand Up To Cancer–Lustgarten Foundation Pancreatic Cancer Interception Dream Team, and co-senior author of the paper. “These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests.”

“Liquid biopsy tests produce promising results for cancer therapy monitoring and disease relapse,” said Lippman, “but,” he added, “they can cause real harm to otherwise healthy people when used for early-disease screening due to unacceptably high false-positive rates that lead to diagnostic tests that are not only expensive, but often dangerous.”

Early cancer detection
Early cancer detection research has yielded tremendous health benefits, Lippman said, resulting in screening methods that detect cancers of the cervix, breast, colon and rectum when they are highly curable. Currently, however, only 5% of pancreatic cancers are diagnosed in stage 1 and only 10% in time for effective surgery. In 2020, 46,774 Americans died of pancreatic cancer, according to the Centers for Disease Control and Prevention.

“Pancreatic cancer has the lowest five-year relative survival rate of all major cancer killers and is the only one for which both the incidence and death rates are increasing,” said Andrew Lowy, MD, clinical director for Cancer Surgery at UC San Diego Health Moores Cancer Center, and chief of Division of Surgical Oncology at UC San Diego School of Medicine.

“Pancreatic cancer is notoriously difficult to detect early, at a stage when surgical resection, the only curative therapy, is possible. At this stage, patients typically have few if any symptoms,” Lowly added.

If study results are validated, Lippman noted, “we can greatly reduce the mortality from this disease which will soon become the second-leading cause of cancer mortality in the U.S.”

Reference
[1] Heitzer E, Perakis S, Geigl JB, Speicher MR. The potential of liquid biopsies for the early detection of cancer. NPJ Precis Oncol. 2017 Oct 17;1(1):36. doi: 10.1038/s41698-017-0039-5. PMID: 29872715; PMCID: PMC5871864.
[2] Blackford AL, Canto MI, Klein AP, Hruban RH, Goggins M. Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis. J Natl Cancer Inst. 2020 Nov 1;112(11):1162-1169. doi: 10.1093/jnci/djaa004. Erratum in: J Natl Cancer Inst. 2021 Feb 1;113(2):216. PMID: 31958122; PMCID: PMC7669234.
[3] Hinestrosa, J.P., Kurzrock, R., Lewis, J.M. et al. Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test. Commun Med 2, 29 (2022). https://doi.org/10.1038/s43856-022-00088-6

Featured image: Blood test. Photo Courtesy: © 2016 – 2022 Fotolia/Adobe. Used with permission.

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