Cronkhite-Canada Syndrome: An investigation in clinical features and pathogenesis.

AIM Cronkhite-Canada syndrome (CCS) is a rare nonhereditary polyposis syndrome and its pathogenesis is poorly understood. This study aimed to investigate the clinical features and potential pathogenesis of CCS. METHODS Eight patients with CCS admitted to our hospital from January 2005 to November 2019 were thoroughly evaluated. Transcriptome profiling was performed on characterizing gastric polyp and normal mucosa from one CCS patient. Differentially expressed genes (DEGs; |logFC|>2, p<0.05) were determined and used in functional analysis. The expression of inhibin βA (INHBA) was further validated in all patients through immunohistochemistry. RESULTS All patients had the clinical manifestations of gastrointestinal polyposis, which was accompanied by diarrhea, skin hyperpigmentation, hair loss, and nail dystrophy. Hyperplastic polyps were observed in seven patients, tubular adenoma in two, inflammatory polyps in one, and hamartomatous polyps in one. All the patients received comprehensive treatment, and four patients achieved clinical remission. A total of 2107 DEGs, 1265 upregulated and 842 downregulated, were found in the gastric polyp compared with normal tissue. Gene Ontology analysis showed that up-regulated genes were significantly enriched in the positive regulation of cell proliferation, epithelium development and angiogenesis. Protein-protein interaction analysis suggested that INHBA was at the center of the interaction network and might play an important role in CCS. The immunohistochemistry results showed that INHBA expression was upregulated in CCS gastric polyps. CONCLUSIONS CCS is a rare disease, and its diagnosis mainly depends on typical clinical manifestations, endoscopic findings, and histological features. Transcriptome profiling and further immunohistochemical verification suggest that INHBA upregulation may contribute to CCS pathogenesis.