Badr Nada, Elshof Luca Ten, Houvast Ruben D, de Muynck Lysanne D A N, Crobach A Stijn L P, van Westen Gerard J P, van Vlierberghe Ronald L P, Mieog J Sven D, Vahrmeijer Alexander L, Kuppen Peter J K
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Sci Rep. 2025 May 16;15(1):17102. doi: 10.1038/s41598-025-00517-1.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of approximately 5-7%, and complete surgical resection remains the only curative treatment but is often unfeasible. Fluorescence-guided surgery (FGS) using tumor-targeted probes may improve tumor visualization and facilitate complete resection. This study aimed to identify and validate tumor targets for FGS during PDAC resection procedures. RNA expression data from over 4000 cell surface genes, obtained from public genomic databases, were analyzed to identify genes encoding PDAC-associated proteins. Eleven potential tumor targets were identified, including CEACAM5, TMPRSS4, COL17A1, CLDN18, and AQP5. Protein expression was evaluated by immunohistochemistry (IHC) in tissues from 44 PDAC and 7 chronic pancreatitis (CP) patients. All targets, except COL17A1, showed significantly higher expression in PDAC tissue compared to healthy pancreatic, CP, and duodenal tissue (p < 0.001), as well as in tumor-positive versus tumor-negative lymph nodes. Especially CEACAM5, TMPRSS4, and AQP5 were identified as the most promising targets for distinguishing PDAC from healthy tissues and detecting lymph node metastasis during FGS. The development of probes targeting multiple markers, such as AQP5 with CEACAM5 and/or TMPRSS4, may help overcome interpatient variability and enhance detection across patients.
胰腺导管腺癌（PDAC）是一种侵袭性恶性肿瘤，5年生存率约为5%-7%，完整的手术切除仍然是唯一的治愈性治疗方法，但往往不可行。使用肿瘤靶向探针的荧光引导手术（FGS）可能会改善肿瘤可视化并促进完整切除。本研究旨在识别和验证PDAC切除手术中FGS的肿瘤靶点。对从公共基因组数据库获得的4000多个细胞表面基因的RNA表达数据进行分析，以识别编码PDAC相关蛋白的基因。确定了11个潜在的肿瘤靶点，包括癌胚抗原相关细胞黏附分子5（CEACAM5）、跨膜丝氨酸蛋白酶4（TMPRSS4）、胶原蛋白17A1（COL17A1）、紧密连接蛋白18（CLDN18）和水通道蛋白-5（AQP5）。通过免疫组织化学（IHC）评估了44例PDAC患者和7例慢性胰腺炎（CP）患者组织中的蛋白表达。除COL17A1外，所有靶点在PDAC组织中的表达均显著高于健康胰腺组织、CP组织和十二指肠组织（p<0.001），在肿瘤阳性与肿瘤阴性淋巴结中也是如此。特别是CEACAM5、TMPRSS4和AQP5被确定为在FGS期间区分PDAC与健康组织以及检测淋巴结转移最有前景的靶点。开发针对多种标志物的探针，如AQP5与CEACAM5和/或TMPRSS4，可能有助于克服患者间的变异性并增强对患者的检测。
