Xu Zhiying, Wang Tao, Song Haiyang, Jiang Xuewen
Department of Nuclear Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264001, P.R. China.
Department of Interventional Therapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264001, P.R. China.
Oncol Lett. 2020 Mar;19(3):2243-2250. doi: 10.3892/ol.2020.11349. Epub 2020 Jan 24.
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 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.
肝内胆管癌（iCCA）是一种起源于肝内胆管的高恶性肿瘤。作为脂筏的一种支架蛋白，flotillin-2在多种癌症中上调，并促进肿瘤进展和转移。据我们所知，本研究首次检测到与配对的相邻非肿瘤组织相比，iCCA组织中flotillin-2上调。此外，免疫组织化学用于研究flotillin-2在由92个iCCA组织组成的微阵列中的表达。总共59个样本（64.1%）表现出flotillin-2高表达，这与淋巴结转移（P=0.029）和肿瘤-淋巴结-转移分期（P=0.016）显著相关。进一步的研究表明，敲低flotillin-2可抑制iCCA细胞系的侵袭能力，进一步支持flotillin-2参与癌症侵袭和转移。此外，Kaplan-Meier分析显示，flotillin-2高表达的患者总体生存结果较差。多变量Cox比例风险模型进一步显示，flotillin-2高表达是iCCA患者预后不良的独立指标（P=0.005）。总体而言，本研究表明，作为侵袭的促进因子和预后不良的独立标志物，flotillin-2可能成为开发iCCA新型治疗药物的潜在靶点。
