Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer
Abstract Pancreatic cysts, particularly intraductal papillary mucinous neoplasms (IPMNs), pose a potential risk for progressing to pancreatic cancer (PC). This study investigates the genetic architecture of benign pancreatic cysts and its potential connection to PC using genome-wide association stud...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-87872-1 |
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| author | A. K. M. Firoj Mahmud Dina Gamaleldin Mansour Aly Yelin Zhao Mikael Benson Martin Smelik Oleg Sysoev Hui Wang Xinxiu Li |
| author_facet | A. K. M. Firoj Mahmud Dina Gamaleldin Mansour Aly Yelin Zhao Mikael Benson Martin Smelik Oleg Sysoev Hui Wang Xinxiu Li |
| author_sort | A. K. M. Firoj Mahmud |
| collection | DOAJ |
| description | Abstract Pancreatic cysts, particularly intraductal papillary mucinous neoplasms (IPMNs), pose a potential risk for progressing to pancreatic cancer (PC). This study investigates the genetic architecture of benign pancreatic cysts and its potential connection to PC using genome-wide association studies (GWAS). The discovery GWAS identified significant genetic variants associated with benign cysts, specifically the rs142409042 variant near the OPCML gene. A pairwise GWAS comparing PC to benign cysts revealed the rs7190458 variant near the BCAR1 and CTRB1 genes. Further analysis with identified GWAS genes highlighted the Actin Related Protein (Arp) 2/3 complex as a potentially important molecular mechanism connecting benign cysts and PC. The Arp2/3 complex-associated genes were significantly upregulated in PC, suggesting their role in the malignant transformation of pancreatic cysts. Differential expression of these genes was observed across various cell types in PC, indicating their involvement in the tumor microenvironment. These findings suggest that the Arp2/3 complex-associated genes can serve as potential biomarkers for predicting the malignant transformation of pancreatic cysts, opening new avenues for targeted therapies and early detection strategies. |
| format | Article |
| id | doaj-art-7ec45bd30c80466db0e63e57ba4e72e2 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7ec45bd30c80466db0e63e57ba4e72e22025-02-02T12:17:43ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87872-1Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancerA. K. M. Firoj Mahmud0Dina Gamaleldin Mansour Aly1Yelin Zhao2Mikael Benson3Martin Smelik4Oleg Sysoev5Hui Wang6Xinxiu Li7Medical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteDivision of Statistics and Machine Learning, Department of Computer and Information Science, Linköping UniversityMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteMedical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska InstituteAbstract Pancreatic cysts, particularly intraductal papillary mucinous neoplasms (IPMNs), pose a potential risk for progressing to pancreatic cancer (PC). This study investigates the genetic architecture of benign pancreatic cysts and its potential connection to PC using genome-wide association studies (GWAS). The discovery GWAS identified significant genetic variants associated with benign cysts, specifically the rs142409042 variant near the OPCML gene. A pairwise GWAS comparing PC to benign cysts revealed the rs7190458 variant near the BCAR1 and CTRB1 genes. Further analysis with identified GWAS genes highlighted the Actin Related Protein (Arp) 2/3 complex as a potentially important molecular mechanism connecting benign cysts and PC. The Arp2/3 complex-associated genes were significantly upregulated in PC, suggesting their role in the malignant transformation of pancreatic cysts. Differential expression of these genes was observed across various cell types in PC, indicating their involvement in the tumor microenvironment. These findings suggest that the Arp2/3 complex-associated genes can serve as potential biomarkers for predicting the malignant transformation of pancreatic cysts, opening new avenues for targeted therapies and early detection strategies.https://doi.org/10.1038/s41598-025-87872-1 |
| spellingShingle | A. K. M. Firoj Mahmud Dina Gamaleldin Mansour Aly Yelin Zhao Mikael Benson Martin Smelik Oleg Sysoev Hui Wang Xinxiu Li Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer Scientific Reports |
| title | Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| title_full | Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| title_fullStr | Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| title_full_unstemmed | Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| title_short | Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| title_sort | proteogenomic analysis reveals arp 2 3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer |
| url | https://doi.org/10.1038/s41598-025-87872-1 |
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