Wang Wen-Quan, Liu Liang, Xu Hua-Xiang, Sun Hui-Chuan, Wu Chun-Tao, Zhu Xiao-Dong, Zhang Wei, Xu Jin, Liu Chen, Long Jiang, Ni Quan-Xing, Tang Zhao-You, Yu Xian-Jun
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; and Pancreatic Cancer Institute, Fudan University, Shanghai, China.
Oncotarget. 2014 Jun 15;5(11):3895-906. doi: 10.18632/oncotarget.2019.
Our previous studies have demonstrated that sorafenib can promote the dissemination of hepatocellular carcinoma (HCC) through downregulation of HTATIP2, a suppressor of tumor growth and metastasis that is associated with inhibition of angiogenesis. Here, we investigated the predictive values of the HTATIP2 level and microvessel density (MVD) with or without sorafenib administration for HCC. Three independent cohorts were included. Using tissue microarray, we assessed the relationship between HTATIP2 expression/MVD and overall survival. The results showed that high HTATIP2 expression and a low MVD value were independent protective prognostic factors after curative HCC resection (297 cases/cohort 1); however, both parameters were converted to independent negative prognostic indicators for patients with postsurgical sorafenib treatment (69/143 cases/cohort 2; P<0.05 for all). This same relationship was observed in patients that received sorafenib treatment for advanced HCC (83 cases/cohort 3; efficacy measures and survival analyses, P<0.05 for all). Moreover, the combination of HTATIP2 and MVD had better power to predict patient death and disease recurrence (P<0.001 for both). We conclude that the combination of HTATIP2 and MVD predicts the converse survival of HCC with or without sorafenib intervention. Our findings can assist in the selection of candidates for personalized treatment with sorafenib.
我们之前的研究表明，索拉非尼可通过下调HTATIP2促进肝细胞癌（HCC）的扩散，HTATIP2是一种肿瘤生长和转移的抑制因子，与抑制血管生成有关。在此，我们研究了无论是否给予索拉非尼，HTATIP2水平和微血管密度（MVD）对HCC的预测价值。纳入了三个独立队列。使用组织芯片，我们评估了HTATIP2表达/MVD与总生存期之间的关系。结果显示，高HTATIP2表达和低MVD值是根治性HCC切除术后（297例/队列1）独立的保护性预后因素；然而，对于接受术后索拉非尼治疗的患者（69/143例/队列2；所有P<0.05），这两个参数均转变为独立的负面预后指标。在接受索拉非尼治疗的晚期HCC患者中（83例/队列3；疗效评估和生存分析，所有P<0.05）也观察到了同样的关系。此外，HTATIP2和MVD的联合在预测患者死亡和疾病复发方面具有更好的效能（两者P<0.001）。我们得出结论，HTATIP2和MVD的联合可预测无论有无索拉非尼干预情况下HCC患者的相反生存情况。我们的研究结果有助于选择索拉非尼个体化治疗的候选患者。
