Serum mucin 5AC (MUC5AC) as a predictor of outcomes and microscopic distant metastasis in pancreatic ductal adenocarcinoma (PDA).

Abstract

767 Background: Our prior studies demonstrated that tissue extracellular MUC5AC (EM) detection (EM-D) is associated with early recurrence, and serum MUC5AC (sM) levels have prognostic value in resected PDA following neoadjuvant therapy. This study evaluates the predictive value of post-operative sM before adjuvant therapy (AT). Methods: Serum samples, collected from January 2010 to June 2021 and sourced from the Ohio State University biorepository, were analyzed using enzyme-linked immunoassays with a human MUC5AC kit (NBP2-76703). Multivariate (MV) Cox regression models quantified progression-free survival (PFS) and overall survival (OS), while Wilcoxon tests compared group differences. Results: Nineteen patients had serum samples available post-operative and pre-AT. The cohort's median age was 65 years (range: 48-83), predominantly Caucasian (n=18), and 58% female. Serum was collected a median of 2 weeks (range: 1-16) after surgery, with a mean sM level of 1.1 ng/mL (range: 0.42 to 3.3). Most patients (17/19) received Gemcitabine-based therapy, one received chemoradiation, and another FOLFIRINOX. Among patients, 3 had no recurrence (Nr), 10 experienced distant metastases only (mets), 3 had local recurrence only (Lr-o), and 3 had both Lr and liver recurrence (Liv/Lr). In the MV model, incorporating sM, EM-D, and AT, higher sM levels (HR=2.83, p=0.04) and negative EM-D (HR=6.85, p=0.02) were associated with increased recurrence risk, whereas AT type did not influence recurrence. Regarding OS, sM was significant (HR=2.95, p=0.04) while other factors were not. Elevated sM levels correlated with metastasis risk (mets vs. Liv/Lr vs. Lr-o vs. Nr = 1.54 vs. 0.61 vs. 0.62 vs. 0.92, p=0.01). Patients with locoregional recurrence had significantly lower sM than those with distant metastasis and no recurrence (mets vs. Liv/Lr+Lr-o vs. Nr = 1.54 vs. 0.62 vs. 0.92, p=0.005). In a separate cohort of 10 metastatic patients (mean sM of 1.8 ng/mL, range: 0.43 to 11.2), liver metastases were linked to significantly lower sM than non-liver metastases (0.54 vs. 3, p=0.02), while peritoneal metastases were associated with higher sM levels (3 vs. 0.6, p=0.04). Conclusions: This small study suggests that sM can serve as a biomarker for assessing outcomes and recurrence sites post resection before the initial dose of AT. Elevated sM should prompt suspicion of microscopic metastases, particularly non-liver metastases.