Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma
Abstract 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...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00517-1 |
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| author | Nada Badr Luca Ten Elshof Ruben D. Houvast Lysanne D. A. N. de Muynck A. Stijn L. P. Crobach Gerard J. P. van Westen Ronald L. P. van Vlierberghe J. Sven D. Mieog Alexander L. Vahrmeijer Peter J. K. Kuppen |
| author_facet | Nada Badr Luca Ten Elshof Ruben D. Houvast Lysanne D. A. N. de Muynck A. Stijn L. P. Crobach Gerard J. P. van Westen Ronald L. P. van Vlierberghe J. Sven D. Mieog Alexander L. Vahrmeijer Peter J. K. Kuppen |
| author_sort | Nada Badr |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-8729a829c11f4ec6b7e93369bb56f5e3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8729a829c11f4ec6b7e93369bb56f5e32025-08-20T03:53:57ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00517-1Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinomaNada Badr0Luca Ten Elshof1Ruben D. Houvast2Lysanne D. A. N. de Muynck3A. Stijn L. P. Crobach4Gerard J. P. van Westen5Ronald L. P. van Vlierberghe6J. Sven D. Mieog7Alexander L. Vahrmeijer8Peter J. K. Kuppen9Department of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterDepartment of Pathology, Leiden University Medical CenterDrug Discovery and Safety, Leiden Academic Centre of Drug ResearchDepartment of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterDepartment of Surgery, Leiden University Medical CenterAbstract 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.https://doi.org/10.1038/s41598-025-00517-1Pancreatic cancerTumor-target selectionFluorescence-guided surgeryData-driven approachMolecular imaging |
| spellingShingle | Nada Badr Luca Ten Elshof Ruben D. Houvast Lysanne D. A. N. de Muynck A. Stijn L. P. Crobach Gerard J. P. van Westen Ronald L. P. van Vlierberghe J. Sven D. Mieog Alexander L. Vahrmeijer Peter J. K. Kuppen Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma Scientific Reports Pancreatic cancer Tumor-target selection Fluorescence-guided surgery Data-driven approach Molecular imaging |
| title | Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| title_full | Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| title_fullStr | Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| title_short | Evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| title_sort | evaluation of tumor targets selected from public genomic databases for imaging of pancreatic ductal adenocarcinoma |
| topic | Pancreatic cancer Tumor-target selection Fluorescence-guided surgery Data-driven approach Molecular imaging |
| url | https://doi.org/10.1038/s41598-025-00517-1 |
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