Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA.
Department of Pathology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA.
Int J Mol Sci. 2024 Aug 20;25(16):9041. doi: 10.3390/ijms25169041.
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 ( = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, = 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, = 0.01). Similar results were noted in a FOLFIRINOX sub-group ( = 36). We established an association of MUC5AC expression with treatment response and outcomes.
新辅助治疗（NAT）在早期胰腺导管腺癌（PDA）中的应用最近受到了关注。我们研究了黏蛋白 5AC（MUC5AC）的临床意义，MUC5AC 有两种主要糖型，一种是糖基化程度较低的不成熟同工型（IM），另一种是高度糖基化的成熟同工型（MM），作为一种在切除的 PDA 中的生物标志物。对 100 例切除的 PDAs 进行免疫组织化学染色，使用各自的单克隆抗体 CLH2（NBP2-44455）和 45M1（ab3649）评估 MUC5AC 的 IM 和 MM 的表达。确定 MUC5AC 的定位（细胞质、顶质和细胞外（EC）），并计算 H 评分。单变量和多变量（MVA）Cox 回归模型用于估计无进展生存期（PFS）和总生存期（OS）。在 100 例切除的 PDA 患者中，43 例接受了 NAT，57 例在接受新辅助治疗前接受了手术（UpS）。在研究人群中（n=100），IM 表达（客观反应 vs. 无反应 vs. UpS 的 H 评分=104 vs. 152 vs. 163，=0.01）和 MM-MUC5AC 检出率（56% vs. 63% vs. 82%，=0.02）差异有统计学意义。在 NAT 组中，根据 MVA（风险比：0.2，95%CI：0.059-0.766，=0.01），MM-MUC5AC 阴性患者的 PFS 明显更好。在 FOLFIRINOX 亚组（n=36）中也观察到了类似的结果。我们建立了 MUC5AC 表达与治疗反应和结果的相关性。
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