Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer

Gastric (GC) and esophageal (EC) cancers are highly lethal. Better understanding of molecular abnormalities is needed for new therapeutic targets and biomarkers to be found. Expression of 18 cancer-related genes in 31 paired normal-tumor samples was quantified by reversely-transcribed quantitative polymerase chain reaction (RTqPCR) and systemic concentration of 27 cytokines/chemokines/growth factors in 195 individuals was determined using Luminex xMAP technology. OnlyKi67,CLDN2,andBCLxLwere altered in GC whileKi67,CDKN1A,ODC1,SLC2A1,HIF1A,VEGFA,NOS2,CCL2,PTGS2,IL10,IL10Ra,andACTA2were changed in EC. The relatively unaltered molecular GC landscape resulted from high expression ofBCLxL,CDKN1A,BCL2,Ki67,HIF1A,VEGFA,ACTA2,TJP1,CLDN2,IL7Ra,ODC1,PTGS2, andCCL2in non-cancerous tissue. TheNOS2expression and IL-4, IL-9, FGF2, and RANTES secretion were higher in cardiac than non-cardiac GC. Four-cytokine panels (interleukin (IL)-1 beta/IL-1ra/IL-6/RANTES or IL-1 beta/IL-6/IL-4/IL-13) differentiated GC from benign conditions with 87-89% accuracy. Our results showed increased proliferative, survival, inflammatory and angiogenic capacity in gastric tumor-surrounding tissue, what might contribute to GC aggressiveness and facilitate cancer recurrence. Further studies are needed to determine theCLDN2andNOS2suitability as candidate molecular targets in GC and cardiac GC, respectively, and discern the role ofCLDN2or to verify IL-1 beta/IL-1ra/IL-6/RANTES or IL-1 beta/IL-6/IL-4/IL-13 usefulness as differential biomarkers.