Abstract 1306P
Background
Pancreatic cancer is one of the deadliest cancers with a 5-year survival rate of only 11%. The potential for curative resection or neoadjuvant therapy increases when the disease is detected early where the 5-year survival increases from 11% to 42%. Because earlier detection of pancreatic ductal adenocarcinoma (PDAC) greatly improves patient outcomes, we conducted a study for the detection of early stage PDAC based on extracellular vesicle (EV)-bound biomarkers from blood plasma.
Methods
EVs were isolated from an initial training cohort consisting of 33 PDAC cases (Stage I = 15, Stage II = 18) and 146 non-PDAC controls. The median age for the cases was 63 years and 73% female while the median age for the non-PDAC controls was 57 years with 47% female population. The isolated EVs were analyzed for protein biomarkers using multiplex ELISAs. To select the most informative biomarkers, forward selection was employed, and a classifier algorithm was built to differentiate PDAC cases from non-PDAC controls. The classifier was then tested using a validation cohort consisting of 51 PDAC cases (Stage I = 16, II = 31, III - IV = 4) and 573 non-PDAC controls, which included 25 benign tumors and 11 pancreatitis subjects. The median age of the validation PDAC cohort was 62 years with a 53% female population while the non-PDAC cohort had a median age of 58 years with a 54% female population.
Results
From the training set, a logistic regression classifier was built with six EV-protein biomarkers providing an AUC of 0.997 (95% CI: 0.978-1.000), with sensitivity of 87.9% (CI:72.7 – 95.2) at a specificity of 99.3% (CI:96.0 – 99.9). After locking the algorithm based on the training set, its performance was tested in a larger validation set yielding an AUC of 0.972 (CI: 0.961 – 0.992), a sensitivity of 80.4% (CI:67.5 – 89.0) and a specificity of 96.0% (CI: 94.0 – 97.3). In the validation set, the stage I sensitivity was 81.2% (CI: 57.0 – 93.4) and the stage II sensitivity was 77.4% (CI:60.2 – 88.6).
Conclusions
These results demonstrate that EV-biomarkers are useful for PDAC early detection. Future studies are aimed to validate the test for high-risk patients (family history of PDAC, known germline mutations, precursor lesions, hereditary pancreatitis, new onset diabetes), as well as to investigate usage in clinical settings.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Biological Dynamics.
Disclosure
J.P. Hinestrosa: Financial Interests, Institutional, Full or part-time Employment: Biological Dynamics. G. Schroeder: Financial Interests, Institutional, Full or part-time Employment: Biological Dynamics. J.M. Lewis: Financial Interests, Institutional, Full or part-time Employment: Biological Dynamics. H. Balcer: Financial Interests, Institutional, Full or part-time Employment: Biological Dynamics. P. Billings: Financial Interests, Institutional, Member of the Board of Directors: Biological Dynamics. All other authors have declared no conflicts of interest.