Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes
Year: 2024
Type: article
Study design: Observational Study
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 heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the 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 (H-scores for objective response vs. no response vs. UpS = 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 according to the 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.
DOI: 10.3390/ijms25169041
Authors: Ashish Manne, Ashwini Kumar Esnakula, Ankur Sheel, Amir Sara, Upender Manne, Ravi Kumar Paluri, Kai He, Wancai Yang, Devendra P Sohal, Anup Kasi, Anne M Noonan, Arjun Mittra, John Hays, Sameek Roychowdhury, Pannaga Malalur, Shafia Rahman, Ning Jin, Jordan M Cloyd, Susan Tsai, Ejaz Aslam, Kenneth Pitter, Eric Miller, Kannan Thanikachalam, Mary Dillhoff, LIanbo Yu
Institutions: The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, University of Alabama at Birmingham, Atrium Health Wake Forest Baptist, Wake Forest Baptist Comprehensive Cancer Center, University of Cincinnati, University of Kansas, The University of Kansas Cancer Center, University of Illinois Chicago, Roswell Park Comprehensive Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,296
Funders: Pelotonia, National Cancer Institute
OpenAlex ID: W4401893970