Prognostic Significance of Serum MUC5AC in Resected Pancreatic Ductal Adenocarcinoma: Initial Insights

Ashish Manne ^1* Yonghua Bao ² Ankur Sheel ¹ Amir Sara ¹ Upender Manne ³ Kannan Thanikachalam ⁴ Ashwini Esnakula ¹ Timothy Pawlik ⁵ Jordan M Cloyd ⁵ Susan Tsai ⁵ Anup Kasi ⁶ Ravi Paluri ⁷ Deepak Sherpally ⁸ Sravan Jeepalyam ⁹ Lianbo Yu ² Wancai Yang ²

• ¹ Comprehensive Cancer Center, The Ohio State University, Columbus, United States
• ² The Ohio State University, Columbus, Ohio, United States
• ³ Division of Anatomic Pathology, Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
• ⁴ Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, New York, United States
• ⁵ Division of Surgical Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States
• ⁶ University of Kansas Hospital, Kansas City, Kansas, United States
• ⁷ Wake Forest University, Winston-Salem, North Carolina, United States
• ⁸ New York Medical College, Valhalla, New York, United States
• ⁹ Stormont Vail Hospital, Topeka, Kansas, United States

We investigated the association between serum MUC5AC (sMUC5AC) levels and patient outcomes among individuals following resection of pancreatic ductal adenocarcinoma (PDA) among patients who had received neoadjuvant therapy (NAT) and upfront surgery (UpS) followed by adjuvant therapy.Methods: Serum samples from the Ohio State University biorepository collected from January 2010 to June 2021 were utilized. The human MUC5AC kit (NBP2-76703) was used to perform enzyme-linked immunoassays to measure sMUC5AC levels. Logistic regression, Cox regression models (univariate and multivariate), recurrence prediction, analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis.Results: In the NAT cohort (n = 23), elevated sMUC5AC levels were significantly (P < 0.05) associated with pathological treatment response, margin positivity, and residual disease. Among 21 patients who had an R0/R1 resection (R2 resection, n=2), higher sMUC5AC levels were associated with shorter progression-free survival (PFS) (HR: 1.64, P = 0.0006) and overall survival (OS) (HR: 1.6, P = 0.005) on univariate analysis. Multivariate models confirmed sMUC5AC as an independent predictor of PFS and OS alongside pathological differentiation and postoperative therapy. Patients with lower sMUC5AC levels had more favorable pathological characteristics, better treatment responses, and improved survival outcomes. These findings were consistent in the FOLFIRINOX subgroup (n = 17). In the UpS cohort (n = 17), post-resection sMUC5AC levels tend to be associated with PFS (P = 0.07) and OS (P = 0.05). Combining sMUC5AC with Carbohydrate antigen (CA) 19-9 enhanced sensitivity (79%) and specificity (67%) to predict recurrence. Higher sMUC5AC levels were associated with earlier recurrence and poor survival outcomes, highlighting its utility in post-surgery risk stratification.Among patients with pre-treatment data (n = 11), sMUC5AC levels were significantly higher among patients with poorly differentiated tumors.This study provides compelling evidence for the clinical utility of sMUC5AC as a prognostic biomarker among patients with resected PDA. Future large-scale studies are needed to validate these findings and establish standard thresholds for sMUC5AC integration into clinical practice.