Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavi-ly-glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of IM and MM isoforms of MUC5AC using respective monoclonal antibodies CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular, EC) was determined, and H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (N=100), IM expression (objective response vs. no response vs. UpS = H-scores 104 vs. 152 vs. 163, p=0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p=0.02) were significantly different. In the NAT-group, MM-MUC5AC-negative patients had significantly better PFS on MVA (Hazard Ratio, 0.2, 95 % CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (N=36). We established an association of MUC5AC expression with treatment response and outcomes.

Background: We explored the potential value of serum MUC5AC (sMUC5AC) as a biomarker to guide perioperative management of early-stage pancreatic ductal adenocarcinoma (PDA) patients receiving neoadjuvant therapy (NAT). Methods: We performed enzyme-linked immunoassays using a human MUC5AC kit (NBP2-76703) in serum samples obtained from The Ohio State University biorepository (between January 2010 and June 2021). Univariate (UV) and multivariate (MV) Cox regression models were used to quantify progression-free survival (PFS); clinical and pathological variables were adjusted in the MV models. UV logistic regression analysis was utilized to examine the association of sMUC5AC with pathological features and survival. 2 Results: Overall, 23 samples (19 FOLFIRINOX, 3 gemcitabine/nab-paclitaxel, 1 FOLFOX) were available for analysis. The median age was 66 years, and 52% were females. sMUC5AC was associated with a) treatment response, margin status, and residual disease (R0 vs. R1/R2) (all P<0.05); b) PFS on both UV (hazard ratio (HR) of 1.4, 95% confidence interval (CI) of 1.07 to 1.82, P=0.01) and MV (HR of 49.2, 95% CI, 4.4 to 1008.3, P=0.002) analyses; and c) PFS in pre-surgery models along with carbohydrate antigen 19-9 (CA19-9) measured on the same day alone (HR of 1.47, 95% CI, 1.06 to 1.93, p=0.04), with CA19-9 on the same day, and NAT regimen (HR of 1.44, 95% CI, 1.12 to 1.93, p=0.01), and with CA19-9 on the same day, NAT regimen, and CA19-9 at diagnosis (HR of 1.52, 95% CI, 1.1 to 2.09, p=0.007). Conclusion: sMUC5AC shows promise to helping to predict outcomes in our preliminary study. Larger prospective studies should validate these findings.