Manne Ashish, Bao Yonghua, Sheel Ankur, Sara Amir, Manne Upender, Thanikachalam Kannan, Esnakula Ashwini, Pawlik Timothy M, Cloyd Jordan M, Tsai Susan, Kasi Anup, Paluri Ravi Kumar, Sherpally Deepak, Jeepalyam Sravan, Yu Lianbo, Yang Wancai
Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States.
Clinical & Translational Science Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Front Oncol. 2025 Apr 7;15:1544928. doi: 10.3389/fonc.2025.1544928. eCollection 2025.
We investigated the association between serum MUC5AC (sMUC5AC) levels and patient outcomes in individuals who underwent resection for pancreatic ductal adenocarcinoma (PDA), including those treated with neoadjuvant therapy (NAT) and those who had upfront surgery (UpS) followed by adjuvant therapy.
Serum samples from the Ohio State University biorepository collected from January 2010 to June 2021 were utilized. The human MUC5AC kit (NBP2-76703) was used to perform enzyme-linked immunoassays to measure sMUC5AC levels. Logistic regression, Cox regression models (univariate and multivariate), recurrence prediction, analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis.
In the NAT cohort (n = 23), elevated sMUC5AC levels were significantly ( < 0.05) associated with pathological treatment response, margin positivity, and residual disease. Among 21 patients who had an R0/R1 resection (R2 resection, n=2), higher sMUC5AC levels were associated with shorter progression-free survival (PFS) (HR: 1.64, = 0.0006) and overall survival (OS) (HR: 1.6, = 0.005) on univariate analysis. Multivariate models confirmed sMUC5AC as an independent predictor of PFS and OS alongside pathological differentiation and postoperative therapy. Patients with lower sMUC5AC levels had more favorable pathological characteristics, better treatment responses, and improved survival outcomes. These findings were consistent in the FOLFIRINOX subgroup (n = 17). In the UpS cohort (n = 17), post-resection sMUC5AC levels tend to be associated with PFS = 0.07) and OS ( = 0.05). Combining sMUC5AC with Carbohydrate antigen (CA) 19-9 enhanced sensitivity (79%) and specificity (67%) to predict recurrence. Higher sMUC5AC levels were associated with earlier recurrence and poor survival outcomes, highlighting its utility in post-surgery risk stratification. Among patients with pre-treatment data (n = 11), sMUC5AC levels were significantly higher among patients with poorly differentiated tumors.
This study provides compelling evidence for the clinical utility of sMUC5AC as a prognostic biomarker among patients with resected PDA. Future large-scale studies are needed to validate these findings and establish standard thresholds for sMUC5AC integration into clinical practice.
我们研究了接受胰腺导管腺癌（PDA）切除术的患者血清MUC5AC（sMUC5AC）水平与患者预后之间的关联，包括接受新辅助治疗（NAT）的患者以及接受 upfront 手术（UpS）后进行辅助治疗的患者。
使用了2010年1月至2021年6月从俄亥俄州立大学生物样本库收集的血清样本。使用人MUC5AC试剂盒（NBP2-76703）进行酶联免疫测定以测量sMUC5AC水平。采用逻辑回归、Cox回归模型（单变量和多变量）、复发预测、方差分析（ANOVA）、t检验和Wilcoxon检验进行统计分析。
在NAT队列（n = 23）中，sMUC5AC水平升高与病理治疗反应、切缘阳性和残留疾病显著相关（<0.05）。在21例接受R0/R1切除的患者（R2切除，n = 2）中，单变量分析显示较高的sMUC5AC水平与较短的无进展生存期（PFS）（HR：1.64，= 0.0006）和总生存期（OS）（HR：1.6，= 0.005）相关。多变量模型证实sMUC5AC与病理分化和术后治疗一起是PFS和OS的独立预测因子。sMUC5AC水平较低的患者具有更有利的病理特征、更好的治疗反应和改善的生存结果。这些发现在FOLFIRINOX亚组（n = 17）中是一致的。在UpS队列（n = 17）中，切除后sMUC5AC水平往往与PFS（= 0.07）和OS（= 0.05）相关。将sMUC5AC与糖类抗原（CA）19-9结合可提高预测复发的敏感性（79%）和特异性（67%）。较高的sMUC5AC水平与较早复发和不良生存结果相关，突出了其在术后风险分层中的效用。在有治疗前数据的患者（n = 11）中，低分化肿瘤患者的sMUC5AC水平显著更高。
本研究为sMUC5AC作为切除PDA患者预后生物标志物的临床效用提供了有力证据。未来需要大规模研究来验证这些发现并建立将sMUC5AC纳入临床实践的标准阈值。
