BackgroundPrevious studies revealed somatic mutations of the cationic trypsinogen gene (PRSS1) in patients with chronic pancreatitis and pancreatic cancer. However, whether PRSS1 mutations trigger pancreatic cancer and/or promote malignant proliferation and metastasis in pancreatic cancer remains largely unclear, as well as the potential underlying mechanisms.MethodsIn the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway.ResultsIt showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct.ConclusionsThese findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an “inside job” role in pancreatic carcinogenesis and tumor development.

中文翻译：

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PRSS1突变：胰腺癌变和胰腺癌的可能发病机制

背景先前的研究揭示了慢性胰腺炎和胰腺癌患者中阳离子胰蛋白酶原基因（PRSS1）的体细胞突变。然而，PRSS1突变是否触发胰腺癌和/或促进胰腺癌的恶性增殖和转移，以及潜在的潜在机制尚不清楚。方法本研究应用全外显子组测序进行筛选，R116C突变为通过 Sanger 测序验证。采用磷酸化抗体阵列、RNA-Seq和RT-qPCR筛选和验证R116C突变通过JAK1-STAT5通路促进胰腺癌进展。与野生型对应物。