Abstract A112: Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection
Authors: Colbatzky Teresa , Al-Shaheri Fawaz N. , Bauer Andrea S. , Giese Nathalia , Hoheisel Jörg D. , Heger Ulrike 
Published: January 2024

Pancreatic ductal adenocarcinoma (PDAC)patients have a 5-year survival rate of less than 10%, partly due to 80% developing recurrence within 2 years after curative intent surgery. As surgical resectability criteria expand and techniques progress, better understanding of tumor biology regarding post-resection prognosis is needed to improve patient outcomes. Our study therefore investigated usefulness of liquid biopsy and proteomics analysis for stratification of post-resection risk groups. Patients undergoing standardized follow-up after resection of PDAC at the European Pancreas Center (Heidelberg, Germany) donated blood samples and clinical data after giving informed consent. Outcomes were extracted from the institutional database or Electronic Health Records and documented retrospectively. From all included patients (n=101) 7mL serum was drawn at different follow-up time points. Overall, 139 samples were collected. Protein expression values of 2953 proteins were determined via antibody microarrays. For analysis and statistics, GenePix 6.0, R and GraphPad Prism were used. First, a principal component analysis was performed on the complete data set. Then the data set was split in a training and test set and A subgroup of 43 patients experienced recurrence of PDAC within 24 months post resection (median: 11.39 months), classified as “early recurrence” (ER). Furthermore, 23 patients experienced recurrence between 26 and 144 months and were termed “late recurrence” (LR). 32 patients had a follow up &gt; 26 months after resection and 6 months after sampling and remained recurrence-free; those were termed “long-term recurrence free survivors” (LT-RFS). Principal component analysis of protein microarray data revealed distinct clustering of LT-RFS together along the primary axis. Contrarily, all of the samples taken at time of recurrence were exclusively found in other quadrants, as were all samples but one of the ER subgroup preceeding diagnosis of recurrence. Samples of the LR subgroup appeared to shift from clustering with LT-RFS samples towards samples from ER and post-recurrence. Lasso regression yielded a panel of 10 proteins, with a specificity of 98.0%/90.9% and a sensitivity of 89.4%/65.0% (training/test set), for identification of samples from LT-RFS. The findings of our protein microarray analysis on PDAC recurrence monitoring suggest a distinct proteome of patients with RFS of &gt;2a post resection. Furthermore, we found hints that the post-resection proteome undergoes a dynamic shift from recurrence-free phenotype towards a phenotype of recurrence. These data need validation in prospective cohorts to determine clinical relevance, however, they point towards opportunities offered by liquid biopsy for sophisticated disease monitoring post resection and for novel insights into mechanisms of disease in PDAC. A protein panel predictive of long-term RFS might enable personalized follow-up pathways and have a positive impact on frequency and invasiveness of post-resection diagnostic testing for PDAC patients.

Citation Format: Teresa Colbatzky, Fawaz N. Al-Shaheri, Andrea S. Bauer, Nathalia Giese, Jörg D. Hoheisel, Ulrike Heger. Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A112.