SERPINA1 promotes the invasion, metastasis, and proliferation of pancreatic ductal adenocarcinoma via the PI3K/Akt/NF-κB pathway.

Serpin peptidase inhibitor clade A member 1 (SERPINA1) is highly expressed in a variety of solid tumors. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we report evidence that SERPINA1 acts as a potent oncogene to drive its extremely malignant character. We found that elevated SERPINA1 expression in primary tumors was associated with lymph node metastasis and shorter survival in PDAC patients. Mechanistic investigations revealed that overexpression of SERPINA1 induced nuclear translocation and phosphorylation of the p65 subunit through the PI3K/Akt/NF-κB pathway, thereby promoting the invasion, metastasis and proliferation of PDAC cells in vitro and in vivo. Conversely, the knockdown of SERPINA1 attenuated this signaling pathway and restored the phenotype of PDAC cells overexpressing SERPINA1. Overall, our study reveals that SERPINA1 affects the properties of PDAC through the PI3K/Akt/NF-κB pathway, and its activation confers the clinical features of epithelial-mesenchymal transition and proliferation in the disease.

The effectiveness of endoscopic ultrasonography findings to distinguish benign and malignant intraductal papillary mucinous neoplasm.

BACKGROUND AND AIMS: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. METHODS: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. RESULTS: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. CONCLUSIONS: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.