Abstract
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. Only Ki67, CLDN2, and BCLxL were altered in GC while Ki67, CDKN1A, ODC1, SLC2A1, HIF1A, VEGFA, NOS2, CCL2, PTGS2, IL10, IL10Ra, and ACTA2 were changed in EC. The relatively unaltered molecular GC landscape resulted from high expression of BCLxL, CDKN1A, BCL2, Ki67, HIF1A, VEGFA, ACTA2, TJP1, CLDN2, IL7Ra, ODC1, PTGS2, and CCL2 in non-cancerous tissue. The NOS2 expression and IL-4, IL-9, FGF2, and RANTES secretion were higher in cardiac than non-cardiac GC. Four-cytokine panels (interleukin (IL)-1β/IL-1ra/IL-6/RANTES or IL-1β/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 the CLDN2 and NOS2 suitability as candidate molecular targets in GC and cardiac GC, respectively, and discern the role of CLDN2 or to verify IL-1β/IL-1ra/IL-6/RANTES or IL-1β/IL-6/IL-4/IL-13 usefulness as differential biomarkers.
Highlights
Gastric cancer (GC) and esophageal cancer (EC) are among the most lethal malignancies worldwide due to delayed diagnosis and lack of effective treatment modalities
Our results show increased proliferative, survival, inflammatory, and angiogenic capacity in gastric tumor-surrounding tissue as compared to esophageal non-cancerous mucosa
It might contribute to GC aggressiveness and facilitate cancer recurrence following curative tumor resection
Summary
Gastric cancer (GC) and esophageal cancer (EC) are among the most lethal malignancies worldwide due to delayed diagnosis and lack of effective treatment modalities. The global effort to eradicate Helicobacter pylori infections, a main risk factor for GC, has caused a decrease in the incidence of a more common distal GC but concomitantly contributed to about seven-fold increase in incidence of its cardia subtype [4]. H. pylori infections are responsible for chronic inflammation and oxidative stress in the gastric mucosa, leading to genetic instability and, to neoplastic transformation [5]. The urgent need for better understanding of the molecular mechanisms underlying the disease is emphasized in hope that it would lead to discovery of new therapeutic strategies, less toxic and more efficient, and improve survival [5]. As the mortality in GC and EC strongly depends on the disease stage at the time of diagnosis [2,7], non-costly and non-invasive tools allowing for early cancer detection are sought after as well
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