MUC5AC糖型在胰腺导管腺癌中的差异表达及诊断价值

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

作者信息

Manne Ashish, Yu Lianbo, Hart Phil A, Tsung Allan, Esnakula Ashwini

机构信息

Department 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, USA.

Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Cancers (Basel). 2023 Oct 2;15(19):4832. doi: 10.3390/cancers15194832.

DOI:10.3390/cancers15194832

PMID:37835525

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10571547/

Abstract

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.

摘要

我们探究了两种重要的粘蛋白5AC（MUC5AC）糖型，即低聚糖基化的未成熟型（IM）和高聚糖基化的成熟型（MM），在包括胰腺导管腺癌（PDA）和神经内分泌肿瘤（NET）在内的肿瘤性疾病（NpD）以及非肿瘤性（非NpD）疾病中的差异表达和诊断价值。利用96例患者构建了市售组织微阵列（TMA），其中包括38例原发性PDA（PT）、5例转移灶（ML）、11例NET，其余为非NpD组织。分别使用CHL2和45M1克隆对IM和MM亚型进行MUC5AC免疫组织化学检测。在非NpD组织中未检测到MUC5AC（两种糖型）。在MUC5AC阳性的肿瘤组织中，IM定位于细胞质（Cy），而MM也在顶端（Ap）和细胞外（Ec）区域被识别。TMA中有一个ML阳性（大网膜）同时表达了两者。对于PDA与非PDA，MM±IM的敏感性（SN）（71%）高于单独的MM（47%）或IM（65%）。单独使用MM时特异性（SP）为100%，加入IM（96%）或单独使用IM（93%）时特异性下降。对于NpD与非NpD，SN（MM + IM - 59%，IM - 55%，MM - 37%）较低，两种糖型（MM±IM）的SP均为100%。MUC5AC糖型的组合对诊断PDA具有高SP和合理的SN。它们有可能成为可靠的诊断标志物，应在更广泛的研究中进一步探究。