The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib
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Wen-Quan Wang1,*, Liang Liu1,*, Hua-Xiang Xu1,*, Hui-Chuan Sun2,*, Chun-Tao Wu1, Xiao-Dong Zhu2, Wei Zhang3, Jin Xu1, Chen Liu1, Jiang Long1, Quan-Xing Ni1, Zhao-You Tang2 and Xian-Jun Yu1
1 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
2 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education, Shanghai, China
3 Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
* These authors contributed equally to this work
Xian-Jun Yu, email:
Keywords: HTATIP2, microvessel density, sorafenib, hepatocellular carcinoma, prognosis
Received: March 26, 2014 Accepted: May 25, 2014 Published: May 27, 2014
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.
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