Quercetin Attenuates Cancer-Associated Fibroblast Activation via Tumor-Stromal Interactions and Demonstrates Its Clinical Value in Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressing malignancy with a poor prognosis. Quercetin is a flavonoid compound with various biological benefits that can be extracted from Chinese herbs or daily foods. Quercetin has anticancer properties in various types of cancers. However, its therapeutic effects and potential mechanisms in PDAC have not been investigated extensively. Here, we confirmed the therapeutic effect of quercetin in PDAC using a mouse model. Based on high-throughput RNA sequencing (RNA-seq) and bioinformatic analysis, we propose that quercetin is involved in stromal infiltration of PDAC. Quercetin attenuates the activation of cancer-associated fibroblasts (CAFs) via tumor-stromal interaction. Meanwhile, we have identified two quercetin-related prognostic models for patients with PDAC. Finally, we proposed a downstream target of quercetin, the ITGB4 gene, which could be a potential therapeutic target for PDAC.