Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and most patients are diagnosed at a stage where the disease is unresectable, locally advanced, or has already metastasized. Invasive pancreatic cancer is believed to arise through a progression of noninvasive ductal le...
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2025-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03810-1 |
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| author | Fereshteh Rezagholizadeh Adel Salimi Ali Sharifi-Zarchi Farid Azmoudeh-Ardalan Kazem Mousavizadeh Fatemeh Tajik Mahshid Panahi Hossein Khorramdelazad Masoud Baghai Wadji Atefeh Kashanizadeh Alireza Lotfalizadeh Seyed Javad Mowla Mohammad Taghi Joghataei |
| author_facet | Fereshteh Rezagholizadeh Adel Salimi Ali Sharifi-Zarchi Farid Azmoudeh-Ardalan Kazem Mousavizadeh Fatemeh Tajik Mahshid Panahi Hossein Khorramdelazad Masoud Baghai Wadji Atefeh Kashanizadeh Alireza Lotfalizadeh Seyed Javad Mowla Mohammad Taghi Joghataei |
| author_sort | Fereshteh Rezagholizadeh |
| collection | DOAJ |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and most patients are diagnosed at a stage where the disease is unresectable, locally advanced, or has already metastasized. Invasive pancreatic cancer is believed to arise through a progression of noninvasive ductal lesions referred to as pancreatic intraepithelial neoplasia (PanIN). The mechanisms driving the transition from PanIN, to invasive PDAC are not fully understood. Moreover, extensive stromal involvement of pancreatic cancer tissue complicates bulk analysis, hindering precise tumor-specific molecular data. Methods This issue was addressed through a comprehensive in-silico analysis of laser-capture microdissected (LCM) pure tumor epithelial cells from transcriptomic PDAC cohort datasets, with survival outcomes further validated using TCGA. We employed LCM to evaluate mRNA expression in PanIN lesions, tumor epithelial, and stromal cells, using RT-qPCR in 20 PDAC patients. Immunohistochemistry (IHC) on 353 PDAC patients, including 73 PanIN lesions and 280 tumor tissues on tissue microarray (TMA) slides, provided further confirmation. Results Based on in-silico analysis, RAD51AP1 was identified as a tumor-specific marker associated with aggressive tumor behavior in captured PDAC samples. RT-qPCR validation demonstrated significantly elevated RAD51AP1 expression in tumor epithelial cells compared to tumor stromal cells, PanIN lesions, and adjacent normal tissues. Consistently, IHC findings for nucleus, cytoplasm, and membrane localization revealed higher RAD51AP1 protein expression in tumor tissues compared to PanIN lesions and normal tissues. This increased expression was correlated with tumor progression and aggressiveness in PDAC patients, as well as reduced survival and poor prognosis in patients with PanIN lesions. Conclusions RAD51AP1 is a tumor-specific molecule that associated with more aggressive behavior, advanced disease, and a worse survival rate. Graphical Abstract |
| format | Article |
| id | doaj-art-d490baf8f56e47419fb08fb5d5c9cbd8 |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-d490baf8f56e47419fb08fb5d5c9cbd82025-08-20T02:39:47ZengBMCCancer Cell International1475-28672025-06-0125112410.1186/s12935-025-03810-1Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancerFereshteh Rezagholizadeh0Adel Salimi1Ali Sharifi-Zarchi2Farid Azmoudeh-Ardalan3Kazem Mousavizadeh4Fatemeh Tajik5Mahshid Panahi6Hossein Khorramdelazad7Masoud Baghai Wadji8Atefeh Kashanizadeh9Alireza Lotfalizadeh10Seyed Javad Mowla11Mohammad Taghi Joghataei12Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical SciencesComputer Engineering Department, Sharif University of TechnologyComputer Engineering Department, Sharif University of TechnologyPathology Department, Imam Khomeini Hospital Complex, Tehran University of Medical SciencesDepartment of Pharmacology, School of Medicine, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesDepartment of Pathology, School of Medicine, Iran University of Medical SciencesDepartment of Immunology, School of Medicine, Rafsanjan University of Medical SciencesDepartment of Surgery, Firoozgar Hospital, Iran University of Medical SciencesDepartment of Surgery, Firoozgar Hospital, Iran University of Medical SciencesCellular and Molecular Research Centre, Iran University of Medical SciencesDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares UniversityCellular and Molecular Research Centre, Iran University of Medical SciencesAbstract Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and most patients are diagnosed at a stage where the disease is unresectable, locally advanced, or has already metastasized. Invasive pancreatic cancer is believed to arise through a progression of noninvasive ductal lesions referred to as pancreatic intraepithelial neoplasia (PanIN). The mechanisms driving the transition from PanIN, to invasive PDAC are not fully understood. Moreover, extensive stromal involvement of pancreatic cancer tissue complicates bulk analysis, hindering precise tumor-specific molecular data. Methods This issue was addressed through a comprehensive in-silico analysis of laser-capture microdissected (LCM) pure tumor epithelial cells from transcriptomic PDAC cohort datasets, with survival outcomes further validated using TCGA. We employed LCM to evaluate mRNA expression in PanIN lesions, tumor epithelial, and stromal cells, using RT-qPCR in 20 PDAC patients. Immunohistochemistry (IHC) on 353 PDAC patients, including 73 PanIN lesions and 280 tumor tissues on tissue microarray (TMA) slides, provided further confirmation. Results Based on in-silico analysis, RAD51AP1 was identified as a tumor-specific marker associated with aggressive tumor behavior in captured PDAC samples. RT-qPCR validation demonstrated significantly elevated RAD51AP1 expression in tumor epithelial cells compared to tumor stromal cells, PanIN lesions, and adjacent normal tissues. Consistently, IHC findings for nucleus, cytoplasm, and membrane localization revealed higher RAD51AP1 protein expression in tumor tissues compared to PanIN lesions and normal tissues. This increased expression was correlated with tumor progression and aggressiveness in PDAC patients, as well as reduced survival and poor prognosis in patients with PanIN lesions. Conclusions RAD51AP1 is a tumor-specific molecule that associated with more aggressive behavior, advanced disease, and a worse survival rate. Graphical Abstracthttps://doi.org/10.1186/s12935-025-03810-1RAD51AP1Pancreatic cancerLaser-captured microdissectionPancreatic intraepithelial neoplasiaMetastasisBiomarker |
| spellingShingle | Fereshteh Rezagholizadeh Adel Salimi Ali Sharifi-Zarchi Farid Azmoudeh-Ardalan Kazem Mousavizadeh Fatemeh Tajik Mahshid Panahi Hossein Khorramdelazad Masoud Baghai Wadji Atefeh Kashanizadeh Alireza Lotfalizadeh Seyed Javad Mowla Mohammad Taghi Joghataei Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer Cancer Cell International RAD51AP1 Pancreatic cancer Laser-captured microdissection Pancreatic intraepithelial neoplasia Metastasis Biomarker |
| title | Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| title_full | Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| title_fullStr | Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| title_full_unstemmed | Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| title_short | Transcriptomic analysis of laser-capture microdissected tumors reveals RAD51AP1 as a tumor-specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| title_sort | transcriptomic analysis of laser capture microdissected tumors reveals rad51ap1 as a tumor specific marker associated progression from pancreatic intraepithelial neoplasia to invasive pancreatic cancer |
| topic | RAD51AP1 Pancreatic cancer Laser-captured microdissection Pancreatic intraepithelial neoplasia Metastasis Biomarker |
| url | https://doi.org/10.1186/s12935-025-03810-1 |
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