Abstract
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.
Highlights
Sorafenib, a receptor tyrosine kinase inhibitor (RTKI) that targets both tumor and endothelial cells, has improved the prognosis for patients with advanced HCC[3, 4].Recently, the use of sorafenib has been investigated for the prevention of postsurgical recurrence and metastasis[5].Despite endeavors to improve the efficacy of sorafenib, the survival benefit of this agent was found to be only a few months, probably due to the lack of effective tools that can assist in patient selection and predict individual outcomes.Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer globally and the third most common cause of cancer-related death[1]
Immunostaining of HIV-1 Tat interactive protein 2 (HTATIP2) was mainly distributed in the cytoplasm of tumor cells or hepatocytes
This was the first report showing that sorafenib directly promoted invasiveness of HCC cells, and we demonstrated its clinical significance in the present study
Summary
A receptor tyrosine kinase inhibitor (RTKI) that targets both tumor and endothelial cells, has improved the prognosis for patients with advanced HCC[3, 4].Recently, the use of sorafenib has been investigated for the prevention of postsurgical recurrence and metastasis[5].Despite endeavors to improve the efficacy of sorafenib, the survival benefit of this agent was found to be only a few months, probably due to the lack of effective tools that can assist in patient selection and predict individual outcomes.Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer globally and the third most common cause of cancer-related death[1]. A receptor tyrosine kinase inhibitor (RTKI) that targets both tumor and endothelial cells, has improved the prognosis for patients with advanced HCC[3, 4]. The use of sorafenib has been investigated for the prevention of postsurgical recurrence and metastasis[5]. Despite endeavors to improve the efficacy of sorafenib, the survival benefit of this agent was found to be only a few months, probably due to the lack of effective tools that can assist in patient selection and predict individual outcomes. The overall survival (OS) rate remains poor, progress has been made recently[2]. Surgical resection of early-stage HCC is the most widely adopted therapy, and a 5-year survival of ~50% can be achieved[2]; the rate of postoperative recurrence or metastasis still remains high
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