Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes
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 (<i>n</i> = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, <i>p</i> = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, <i>p</i> = 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, <i>p</i> = 0.01). Similar results were noted in a FOLFIRINOX sub-group (<i>n</i> = 36). We established an association of MUC5AC expression with treatment response and outcomes.
Authors
- John L. Hays (ORCID: https://orcid.org/0000-0003-3140-8677)
- Anup Kasi (ORCID: https://orcid.org/0000-0002-4305-5701)
- Anne M. Noonan (ORCID: https://orcid.org/0000-0001-8083-8492)
- Ashwini Kumar Esnakula (ORCID: https://orcid.org/0000-0001-6029-0124)
- Lianbo Yu
- Upender Manne (ORCID: https://orcid.org/0000-0002-1545-3032)
- Ravi Kumar Paluri (ORCID: https://orcid.org/0000-0002-2317-7082)
- Pannaga Malalur (ORCID: https://orcid.org/0000-0002-9222-4321)
- Eric David Miller (ORCID: https://orcid.org/0000-0002-4931-3521)
- Amir Sara
- Arjun Mittra (ORCID: https://orcid.org/0000-0001-9572-3495)
- Ashish Manne (ORCID: https://orcid.org/0000-0003-2356-5162)
- Kenneth L. Pitter (ORCID: https://orcid.org/0000-0002-9450-313X)
- Ning Jin (ORCID: https://orcid.org/0000-0002-6689-4671)
- Jordan M. Cloyd (ORCID: https://orcid.org/0000-0002-2373-8433)
- Davendra Sohal (ORCID: https://orcid.org/0000-0002-0182-8403)
- Aslam M. Ejaz (ORCID: https://orcid.org/0000-0002-1387-2604)
- Wancai Yang (ORCID: https://orcid.org/0000-0001-7437-9197)
- Shafia Rahman (ORCID: https://orcid.org/0000-0003-4751-0852)
- Kai He (ORCID: https://orcid.org/0000-0002-5805-3354)
- Kannan Thanikachalam (ORCID: https://orcid.org/0000-0001-5379-8966)
- Sameek Roychowdhury (ORCID: https://orcid.org/0000-0002-8297-3038)
- Ankur Sheel (ORCID: https://orcid.org/0000-0003-3408-8445)
- Mary Dillhoff
- Susan Tsai
Institutions
- Atrium Health Wake Forest Baptist (US)
- Roswell Park Comprehensive Cancer Center (US)
- University of Illinois Urbana-Champaign (US)
- Illinois College (US)
- University of Alabama at Birmingham (US)
- University of Illinois Chicago (US)
- The University of Kansas Cancer Center (US)
- Wake Forest Baptist Comprehensive Cancer Center
- The Ohio State University (US)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-08-20
- DOI
- https://doi.org/10.3390/ijms25169041
- Citations
- 3
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.85