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

Abstract

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.