Upregulation of Connexin 30 in Intestinal Phenotype Gastric Cancer and Its Reduction during Tumor Progression

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Aims: The mucin phenotype is associated with clinicopathological findings and tumorigenesis in gastric cancer (GC). The aim was to search for a novel marker regulating the intestinal phenotype of GC. Methods and Results: We performed microarray analyses, and GJB6 (encoding connexin 30) was identified as a gene associated with the intestinal phenotype. Immunostaining of connexin 30 in 169 GC cases revealed that 47 (28%) cases were positive for connexin 30, while connexin 30 was negative in nonneoplastic gastric tissue. Connexin 30-negative GC cases showed more advanced T grade, N grade, and tumor stage than connexin 30-positive GC cases. Six (13%) GC cases positive for connexin 30 were histologically of the differentiated type. In addition, the expression of gastric and intestinal phenotypes of GC was examined by immunostaining for MUC5AC, MUC6, MUC2, and CD10. Connexin 30 expression occurred more frequently in the intestinal phenotype (48%) than in other phenotypes (21%) of GC. Conclusion: These results indicate that the expression of connexin 30 is a novel differentiation marker mediating the biological behavior of intestinal phenotype GC.