Serum MUC5AC as a dynamic biomarker for tumor response, prognosis, and risk stratification in resected pancreatic ductal adenocarcinoma.

Abstract

e16364 Background: There is an unmet need for novel biomarkers to guide and personalize treatment strategies for early-stage pancreatic ductal adenocarcinoma (PDA), specifically in determining whether upfront surgery (UpS) or neoadjuvant therapy (NAT) is the optimal approach. Our prior work demonstrated that extracellular MUC5AC (EC-M) in resected samples and serum MUC5AC (S-M) during NAT predict outcomes with limited utility in the UpS group. We hypothesized that S-M is a dynamic biomarker with significance varying by stage of treatment and surgery. This study evaluates S-M’s correlation with key clinical and pathological features across three stages: at diagnosis (Dx), during NAT, and postoperatively in the UpS group. Methods: Resected tissue and serum samples from PDA patients (2010–2021) were obtained from the Ohio State University biorepository. Enzyme-linked immunoassays (NBP2-76703) quantified S-M levels, and immunohistochemistry using 45M1 monoclonal antibody (ab3649) determined tissue MUC5AC localization and H-scores. Logistic regression was employed to assess correlations between S-M and other parameters. Kaplan-Meier methods estimated progression-free survival (PFS), and median survival times were compared using the log-rank test. Results: The study included 51 patients stratified by serum sample availability: Dx (n = 11), during NAT (n = 23, median 5 weeks of therapy), and Post-UpS (n = 17, median 8 weeks post-surgery). In the Dx group, 2 had UpS, and 9 had NAT. In the NAT group, most patients received FOLFIRINOX as their NAT, whereas gemcitabine-based regimens were more commonly used in the UpS group. Key results are discussed in the table below. Mean S-M was used to compare groups. The primary limitations of this study include the small sample size and the heterogeneity in perioperative therapy regimens among patients. Conclusions: S-M is a dynamic biomarker that correlates with tumor and treatment-related changes, especially during NAT and post-surgery. S-M has strong prognostic value for PFS and OS and may serve as a risk stratification tool for distant metastases post-surgery. Further studies with larger cohorts and serial sampling are warranted to validate these findings. Post-UpS During NAT Dx Serum CA19-9 on the same day Not significant (NS) NS Direct correlation (DC) (p=0.007) Tissue 45M1 expression (H-score) NS DC (0.04) NS EC MUC5AC detection, yes vs. no NS 2.4 vs. 0.9 (0.05) NS Median PFS in months (m),< vs. ≥ median 14.8, 1.5 vs. 0.79 (0.05)(n=8 vs. 9) 7.6, 2.8 vs. 0.8 (0.01)(n=11 vs. 12) NS Median OS in m,< vs. ≥ median 25.8, 0.8 vs. 1.5 (0.02)(n=8 vs. 9) NS NS Distant metastasis vs. local or no recurrence 1.5 vs 0.75 (0.01)(n=9 vs. 8) NS NS Margins status, positive vs. negative NS 2.7 vs. 0.67 (0.002)(n=13 vs. 10) NS Response – near complete vs. partial vs. none Not applicable 0.43 vs. 2.8 vs. 1.2 (0.02)(n= 2 vs. 9 vs. 12) NS in NAT