Abstract
We have previously reported that Cezanne could be a prognostic biomarker for survival in hepatocellular carcinoma (HCC) patients. However, the role of Cezanne genes in HCC cells and its response to postoperative adjuvant transcatheter arterial chemoembolization (TACE) in HCC patients remains unknown. In this study, Cezanne expression was detected in human HCC using real-time PCR, western blot and immunohistochemistry. The function of Cezanne in HCC cells was determined by Transwell invasion assays and nude mice metastasis assay. The response of Cezanne in patients who received adjuvant TACE after hepatectomy was evaluated. Functional study demonstrated that interference of Cezanne expression promoted the migration and invasion of HCC cells in vitro and boosted metastasized HCC formation in mice. Upregulation of Cezanne diminished the adhesion and migration of hepatoma cells. Further study indicated that Cezanne might inhibit invasion of HCC cells by inducing epithelial–mesenchymal transition (EMT). In addition, patients with low Cezanne expression had significant improvement in prognosis after receiving adjuvant TACE. In contrast, patients with high Cezanne expression had a poorer response to adjuvant TACE. Moreover, Cezanne status was associated with response to adjuvant TACE in patients subgroup stratified by vascular invasion, tumor size and tumor number. In conclusion, Cezanne may be a novel antioncogene that has a pivotal role in the invasion of HCC and contribute to the selection of patients who may benefit from adjuvant TACE to prevent recurrence.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common solid tumors and prevalent fatal cancers worldwide, especially in East Asia and Sub-Saharan Africa.[1,2] HCC generally arises in cirrhotic livers and has a poor prognosis because of the high incidence of disease recurrence after curative treatment.[3,4] the prevention of recurrence constitutes one of the most important challenges in improving surgical efficacy
Our previous results had reported that Cezanne has a pivotal role in tumor progression and prognosis, and may act as a potential prognostic biomarker for survival in HCC patients
We further investigated the role of Cezanne in tumor cell migration and invasion in HCC cells
Summary
Hepatocellular carcinoma (HCC) is one of the most common solid tumors and prevalent fatal cancers worldwide, especially in East Asia and Sub-Saharan Africa.[1,2] HCC generally arises in cirrhotic livers and has a poor prognosis because of the high incidence of disease recurrence after curative treatment.[3,4] the prevention of recurrence constitutes one of the most important challenges in improving surgical efficacy. Systemic chemotherapy and transcatheter arterial chemoembolization (TACE) are the commonly used adjuvant managements in preventing recurrence and prolonging the survival of patients after hepatectomy. Cezanne may act as a potential prognostic biomarker for survival in HCC patients.[17] we hypothesized that the effect of postoperative adjuvant TACE on survival in patients with low Cezanne expression may differ from those with high Cezanne expression. We evaluated the role of Cezanne genes in HCC and its response to postoperative adjuvant TACE in HCC patients
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