Preprint Article Version 1 This version is not peer-reviewed

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts the Treatment Response And Outcomes

Version 1 : Received: 6 July 2024 / Approved: 7 July 2024 / Online: 8 July 2024 (16:12:41 CEST)

How to cite: Manne, A.; Esnakula, A. K.; Sheel, A.; Sara, A.; Manne, U.; Paluri, R. K.; He, K.; Yang, W.; Sohal, D. P.; Kasi, A.; Noonan, A. M.; Mittra, A.; Hays, J.; Roychowdhury, S.; Malalur, P.; Rahman, S.; Jin, N.; Cloyd, J. M.; Tsai, S.; Aslam, E.; Pitter, K.; Miller, E.; Thanikachalam, K.; Dillhoff, M.; Yu, L. Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts the Treatment Response And Outcomes. Preprints 2024, 2024070605. https://doi.org/10.20944/preprints202407.0605.v1 Manne, A.; Esnakula, A. K.; Sheel, A.; Sara, A.; Manne, U.; Paluri, R. K.; He, K.; Yang, W.; Sohal, D. P.; Kasi, A.; Noonan, A. M.; Mittra, A.; Hays, J.; Roychowdhury, S.; Malalur, P.; Rahman, S.; Jin, N.; Cloyd, J. M.; Tsai, S.; Aslam, E.; Pitter, K.; Miller, E.; Thanikachalam, K.; Dillhoff, M.; Yu, L. Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts the Treatment Response And Outcomes. Preprints 2024, 2024070605. https://doi.org/10.20944/preprints202407.0605.v1

Abstract

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.

Keywords

pancreatic adenocarcinoma; MUC5AC; neoadjuvant therapy; prognosis; recurrence; resectable pancreatic cancer; predictive biomarker

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

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