每肿瘤体积的循环骨桥蛋白作为可切除性肝内胆管癌的预后生物标志物。
Circulating osteopontin per tumor volume as a prognostic biomarker for resectable intrahepatic cholangiocarcinoma.
作者信息
Zhou Kai-Qian, Liu Wei-Feng, Yang Liu-Xiao, Sun Yun-Fan, Hu Jie, Chen Fei-Yu, Zhou Cheng, Zhang Xiang-Yu, Peng Yuan-Fei, Yu Lei, Zhou Jian, Fan Jia, Wang Zheng
机构信息
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.
出版信息
Hepatobiliary Surg Nutr. 2019 Dec;8(6):582-596. doi: 10.21037/hbsn.2019.03.14.
BACKGROUND
The role of osteopontin (OPN) in intrahepatic cholangiocarcinoma (ICC) remains controversial. This study aimed to explore the prognostic value of OPN in patients with ICC undergoing curative resection.
METHODS
Patients undergoing curative resection from 2005 to 2016 were identified for inclusion in this retrospective study. The expression level of OPN in tumors was measured in each of the 228 patients by immunohistochemistry. Circulating OPN in serum was tested in 124 patients by ELISA. Tumor volume was calculated according to preoperative imaging or operation record. Proliferation assay, wound healing assay, and invasion assay were performed to investigate the biological function.
RESULTS
Low expression of OPN in tissue was associated with lymph node metastasis (P=0.009) and shorter overall survival (OS) (P=0.001). A low level of circulating OPN/volume was associated with multiple tumors (P<0.001), vascular invasion (P=0.027), visceral peritoneal perforation (P=0.001), and lymph node metastasis (P=0.002). It was also able to predict the invasive behavior, lymph node metastasis, and early recurrence with the area under the receiver operating curve (AUC) of being 0.719, 0.708 and 0.622 respectively. Patients with a low level of circulating OPN/volume had shorter OS (P=0.028) and disease-free survival (DFS) (P=0.004) and could benefit from adjuvant chemotherapy (P=0.011). Compared with negative controlled cells, ICC cell lines, which expressed more OPN, showed a decelerated proliferation rate, the weaker ability of migration and invasion, while the opposite was true for the cells expressed less OPN. , , and were negatively regulated by OPN.
CONCLUSIONS
A low level of circulating OPN/volume could indicate aggressive characteristics, along with poor prognosis and efficacy of adjuvant chemotherapy in ICC patients. Over expression of OPN may inhibit phenotypes facilitating ICC metastasis by negatively regulating , , and .
背景
骨桥蛋白（OPN）在肝内胆管癌（ICC）中的作用仍存在争议。本研究旨在探讨OPN在接受根治性切除的ICC患者中的预后价值。
方法
确定2005年至2016年接受根治性切除的患者纳入本回顾性研究。通过免疫组织化学检测228例患者肿瘤中OPN的表达水平。通过ELISA检测124例患者血清中的循环OPN。根据术前影像学或手术记录计算肿瘤体积。进行增殖试验、伤口愈合试验和侵袭试验以研究其生物学功能。
结果
组织中OPN低表达与淋巴结转移（P = 0.009）和总生存期（OS）较短（P = 0.001）相关。循环OPN/体积水平低与多发肿瘤（P < 0.001）、血管侵犯（P = 0.027）、脏腹膜穿孔（P = 0.001）和淋巴结转移（P = 0.002）相关。它还能够预测侵袭行为、淋巴结转移和早期复发，受试者工作特征曲线（ROC）下面积分别为0.719、0.708和0.622。循环OPN/体积水平低的患者OS较短（P = 0.028）和无病生存期（DFS）较短（P = 0.004），并且可以从辅助化疗中获益（P = 0.011）。与阴性对照细胞相比，表达更多OPN的ICC细胞系显示增殖速率减慢、迁移和侵袭能力较弱，而表达较少OPN的细胞则相反。 、 和 受OPN负调控。
结论
循环OPN/体积水平低可能表明ICC患者具有侵袭性特征、预后不良以及辅助化疗效果不佳。OPN的过表达可能通过负调控 、 和 来抑制促进ICC转移的表型。
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