Increased Expression of Two Alternative Spliced Variants of CD1d Molecule in Human Gastric Cancer

Abstract

<b>Background</b>: CD1d presents glycolipid antigens to invariant natural killer T (iNKT) cells. The role of CD1d in the development of peptic ulcer and gastric cancer has not been revealed, yet. <br/><b>Objective</b>: To clarify the expression of alternatively spliced variants of CD1d in peptic ulcer and gastric cancer. <br/><b>Methods</b>: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC), according to their endoscopic and histopathological examinations. H. pylori infection was diagnosed by rapid urease test and histopathology. The expression levels of V2, V4, and V5 spliced variants of CD1d molecule were determined by quantitative Reverse Transcriptase PCR. <br/><b>Results</b>: Relative gene expression levels of V4 were higher in GC patients (n=37) than those in NUD (n=49) and PUD (n=51) groups (p<0.05 and p<0.01, respectively). Moreover, GC patients showed higher expression levels of V5 compared to NUD and PUD groups (p<0.001 and p<0.001, respectively). Positive correlation coefficients were attained between V4 and V5 expression in patients with PUD (r=0.734, p<0.0001) and GC (r=0.423, p<0.01), but not in patients with NUD. Among NUD patients, the expression levels of V4, but not V5, were higher in H. pylori-positive patients than in H. pylorinegative ones (p<0.01). <br/><b>Conclusion</b>: Collectively, both membrane-bound (V4) and soluble (V5) isoforms of CD1d were over-expressed in gastric tumor tissues, suggesting that they are involved in anti-tumor immune responses.