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<p>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 <i>OPCML</i> gene. A pairwise GWAS comparing PC to benign cysts revealed the rs7190458 variant near the <i>BCAR1</i> and <i>CTRB1</i> 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.</p>

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Proteogenomic analysis reveals Arp 2/3 complex as a common molecular mechanism in high risk pancreatic cysts and pancreatic cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月31日

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  • A. K. M. Firoj Mahmud,
  • Dina Gamaleldin Mansour Aly,
  • Yelin Zhao,
  • Mikael Benson,
  • Martin Smelik,
  • Oleg Sysoev,
  • Hui Wang,
  • Xinxiu Li

摘要

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.