Flotillin-2 predicts poor prognosis and promotes tumor invasion in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant neoplasm arising from the intrahepatic bile ducts. As a scaffold protein of lipid rafts, flotillin-2 is upregulated in several types of cancer and promotes tumor progression and metastasis. To the best of our knowledge, the present study was the first to detect the upregulation of flotillin-2 in iCCA tissues compared with matched adjacent non-tumor tissues. In addition, immunohistochemistry was used to investigate the expression of flotillin-2 in a microarray consisting of 92 iCCA tissues. A total of 59 samples (64.1%) exhibited high flotillin-2 expression, which was significantly related to lymph node metastasis (P=0.029) and tumor-node-metastasis stage (P=0.016). Further in vitro study demonstrated that knockdown of flotillin-2 inhibited the invasive capability of iCCA cell lines, further supporting the participation of flotillin-2 in cancer invasion and metastasis. Moreover, Kaplan-Meier analysis showed patients with high flotillin-2 expression had worse overall survival outcomes. The multivariate Cox proportional hazards model further revealed that high flotillin-2 expression was an independent indicator (P=0.005) of poor prognosis for patients with iCCA. Collectively, the present study revealed that as a promoter of invasion and an independent marker of poor prognosis, flotillin-2 may serve as a potential target for the development of novel therapeutic agents for iCCA.