Multiple pathways, including the signal transducer and activator of transcription 3 (STAT3), Helicobacter pylori (H. pylori), the PI3K/Akt pathway, toll-like receptor 2 (TLR2), caudal-type homeobox 2 (Cdx2), Snail, E-cadherin, MMP, and CpG island hypermethylation, are all associated with CLDN-4 expression in precancerous GC lesions [30]. This evidence concerns the gene CDH1 and gastric cancer.