Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma

We explored the differential expression and diagnostic value of two significant Mucin 5AC (MUC5AC) glycoforms, less-glycosylated immature (IM) and heavily-glycosylated mature (MM), in neoplastic diseases (NpD), including pancreatic ductal adenocarcinoma (PDA) and neuroendocrine tumors (NET), and non...

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Main Authors: Ashish Manne, Lianbo Yu, Phil A Hart, Allan Tsung, Ashwini Esnakula
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/19/4832
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author Ashish Manne
Lianbo Yu
Phil A Hart
Allan Tsung
Ashwini Esnakula
author_facet Ashish Manne
Lianbo Yu
Phil A Hart
Allan Tsung
Ashwini Esnakula
author_sort Ashish Manne
collection DOAJ
description We explored the differential expression and diagnostic value of two significant Mucin 5AC (MUC5AC) glycoforms, less-glycosylated immature (IM) and heavily-glycosylated mature (MM), in neoplastic diseases (NpD), including pancreatic ductal adenocarcinoma (PDA) and neuroendocrine tumors (NET), and non-neoplastic (non-NpD) diseases. Commercially available tissue microarray (TMA) was constructed from 96 patients, including 38 primary PDA (PT), 5 metastatic lesions (ML), 11 NET, and the rest being non-NpD tissues. Immunohistochemistry for MUC5AC was performed using CHL2 and 45M1 clones for IM and MM isoforms, respectively. MUC5AC (both glycoforms) are not detected in non-NpD. In MUC5AC-positive neoplastic tissues, IM was localized to the cytoplasm (Cy) while MM was identified in apical (Ap) and extracellular (Ec) regions too. One ML positive (omentum) in the TMA expressed both. For PDA vs. non-PDA, the sensitivity (SN) was higher with MM ± IM (71%) than MM (47%) or IM (65%)-alone. The specificity (SP) was 100% with MM-alone, which dropped with the addition of IM (96%) or IM-alone (93%). For NpD vs. non-NpD, the SN (MM + IM-59%, IM-55%, MM-37%) was inferior, and SP was 100% for both glycoforms (MM ± IM). The combination of MUC5AC glycoforms has high SP and reasonable SN to diagnose PDA. They have the potential to be a reliable diagnostic marker and should be investigated further in more extensive studies.
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spelling doaj.art-9dd31d34bde14e698c01097b2314bf5e2023-11-19T14:11:12ZengMDPI AGCancers2072-66942023-10-011519483210.3390/cancers15194832Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal AdenocarcinomaAshish Manne0Lianbo Yu1Phil A Hart2Allan Tsung3Ashwini Esnakula4Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USADepartment of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USADivision of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Surgery, University of Virginia Health, Charlottesville, VA 22908, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USAWe explored the differential expression and diagnostic value of two significant Mucin 5AC (MUC5AC) glycoforms, less-glycosylated immature (IM) and heavily-glycosylated mature (MM), in neoplastic diseases (NpD), including pancreatic ductal adenocarcinoma (PDA) and neuroendocrine tumors (NET), and non-neoplastic (non-NpD) diseases. Commercially available tissue microarray (TMA) was constructed from 96 patients, including 38 primary PDA (PT), 5 metastatic lesions (ML), 11 NET, and the rest being non-NpD tissues. Immunohistochemistry for MUC5AC was performed using CHL2 and 45M1 clones for IM and MM isoforms, respectively. MUC5AC (both glycoforms) are not detected in non-NpD. In MUC5AC-positive neoplastic tissues, IM was localized to the cytoplasm (Cy) while MM was identified in apical (Ap) and extracellular (Ec) regions too. One ML positive (omentum) in the TMA expressed both. For PDA vs. non-PDA, the sensitivity (SN) was higher with MM ± IM (71%) than MM (47%) or IM (65%)-alone. The specificity (SP) was 100% with MM-alone, which dropped with the addition of IM (96%) or IM-alone (93%). For NpD vs. non-NpD, the SN (MM + IM-59%, IM-55%, MM-37%) was inferior, and SP was 100% for both glycoforms (MM ± IM). The combination of MUC5AC glycoforms has high SP and reasonable SN to diagnose PDA. They have the potential to be a reliable diagnostic marker and should be investigated further in more extensive studies.https://www.mdpi.com/2072-6694/15/19/4832pancreatic cancermucinMUC5AC45M1CLH2pancreatic ductal adenocarcinoma
spellingShingle Ashish Manne
Lianbo Yu
Phil A Hart
Allan Tsung
Ashwini Esnakula
Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
Cancers
pancreatic cancer
mucin
MUC5AC
45M1
CLH2
pancreatic ductal adenocarcinoma
title Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
title_full Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
title_fullStr Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
title_short Differential Expression and Diagnostic Value of MUC5AC Glycoforms in Pancreatic Ductal Adenocarcinoma
title_sort differential expression and diagnostic value of muc5ac glycoforms in pancreatic ductal adenocarcinoma
topic pancreatic cancer
mucin
MUC5AC
45M1
CLH2
pancreatic ductal adenocarcinoma
url https://www.mdpi.com/2072-6694/15/19/4832
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