Elevated expression of Gsα in intrahepatic cholangiocarcinoma associates with poor prognosis

BACKGROUND: The stimulatory G protein a subunit (G(s)alpha) plays important roles in diverse cell processes including tumorigenesis. Activating mutations in G(s)alpha gene (GNAS) have been reported to be associated with poor prognosis in various human carcinomas. Furthermore, G(s)alpha signaling is crucial in promoting liver regeneration by interacting with growth factor signaling, indicating that G(s)alpha might play a promoting role in cancer development. However, little is known about the correlation between G(s)alpha levels and clinicopathological parameters in intrahepatic cholangiocarcinoma (ICC). METHODS: We performed immunoblotting to examine the expression levels of G(s)alpha and Ki67 proteins in tumor tissues and the corresponding adjacent tissues. A total of 74 pair of specimens resected from 74 ICC patients were examined. The association between G(s)alpha levels and clinicopathological findings and prognosis of the patients was evaluated. RESULTS: Western blotting demonstrated that the expression of G(s)alpha was significantly higher in ICC tissues compared with that in their corresponding adjacent tissues. G(s)alpha protein was highly expressed in about half of ICC tissues (48.6%, 36/74) while only 28.4% (21/74) of tumor adjacent tissues showed G(s)alpha high expression (P=0.011). High G(s)alpha expression in ICC was significantly associated with the numbers of tumor nodules (P=0.037) and lymph node metastases (P=0.010). Moreover, the level of G(s)alpha was significantly and positively correlated with Ki67 expression (P<0.001). In addition, the recurrence-free survival rate and overall survival rate in the G(s)alpha high group were significantly lower than those in the G(s)alpha low group (P=0.004 and P=0.005, respectively). CONCLUSIONS: High G(s)alpha expression is correlated with poor prognosis in ICC patients. G(s)alpha might serve as a potential prognostic indicator of ICC.