Identification of CLDN18 as a potential diagnostic biomarker and therapeutic target for pancreatic cancer based on multiomic analysis

Abstract Background Claudin 18 (CLDN18) is a transmembrane protein localized in the apical regions to form a tight-junction complex. The expression of CLDN18 was restricted to normal lung and stomach tissues but was aberrantly activated in some types of cancers, and this molecule can serve as a promising target for targeted treatment. Methods The mRNA expression, genetic variations and prognostic values of CLDN18 in pancreatic cancer (PC) were analyzed using public data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA) databases and multiple online tools. The role of cyclic AMP-responsive element binding protein (CREB) and DNA methylation in regulating the expression of CLDN18 was determined by correlation analysis. Results The expression of CLDN18 was restricted to the lung and stomach in normal tissues, but was ectopically overexpressed in PC. CLDN18 mRNA expression was higher in cancers with advanced local invasion, later clinical stage, infiltrating duct or mucinous carcinoma types. Genetic variations of CLDN18 are rarely observed in PC. Correlation analysis revealed that CREB3L1, CREB3L3, and CREB3L4 were significantly positively coexpressed with CLDN18, and CLDN18 expression increased as methylation gradually decreased. The expression of CLDN18 was not observed to plays a role in predicting the survival of PC patients. Conclusions This data-driven study summarizes the expression features of CLDN18 in PC and demonstrates that it may serve as an ideal biomarker and therapy target for PC.