Hongyang Deng,1 Qi Xiao,1 Xiaodong Xu,1 Lingyi Zhang,2 Youcheng Zhang1 

1Department of General Surgery, Hepatic-Biliary-Pancreatic Institute, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Liver Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China

Correspondence: Youcheng Zhang, Department of General Surgery, Hepatic-biliary-pancreatic Institute, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China, Email zhangyouchengphd@163.com

Background: The family with the sequence similarity 198 member B (FAM198B) has been found to contribute to the progression of gastric cancer (GC). However, the role and molecular mechanism of FAM198B in GC remains poorly understood. This work found a link between FAM198B and quercetin, and the regulatory effect of FAM198B on the MAPK pathway of GC.
Methods: FAM198B expression was identified through multiple public data sets and verified in clinical tissue samples. The associations between FAM198B and the prognosis of patients with GC were analyzed via the Kaplan‒Meier plotter and Cox regression analysis. Gene set enrichment analysis, coexpressed genes, and RNA sequencing were used to explore the related functions and signaling pathways of FAM198B in GC. In vitro assays assessed the effects of FAM198B knockdown on GC cells. FAM198B was found as a quercetin target by the HERB database and in vitro assays.
Results: FAM198B was highly expressed in tissues from GC patients (p< 0.001) and was positively associated with poor prognosis (p< 0.001) and immune cell infiltration in GC patients. FAM198B knockdown inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells (all p< 0.05). In addition, FAM198B knockdown decreased the phosphorylation of p-Erk1/2 and p-p38 in GC cells (all p< 0.01). Quercetin inhibited FAM198B expression and the phosphorylation of p-Erk1/2 and p-p38 in GC cells (all p< 0.05).
Conclusion: Quercetin inhibits the proliferation, migration, invasion, and EMT of GC cells by inhibiting the FAM198B/MAPK signaling pathway. These discoveries lay the groundwork for developing the treatment of GC by quercetin and targeting FAM198B. In the future, more preclinical and clinical studies are needed to confirm the efficacy and safety of quercetin and target FAM198B in GC.

Keywords: FAM198B, quercetin, MAPK signaling pathway, EMT, proliferation, migration, invasion, gastric cancer