PT - JOURNAL ARTICLE AU - Jean-Pierre Gillet AU - Jesper B. Andersen AU - James P. Madigan AU - Sudhir Varma AU - Rachel K. Bagni AU - Katie Powell AU - William E. Burgan AU - Chung-Pu Wu AU - Anna Maria Calcagno AU - Suresh V. Ambudkar AU - Snorri S. Thorgeirsson AU - Michael M. Gottesman TI - A Gene Expression Signature Associated with Overall Survival in Patients with Hepatocellular Carcinoma Suggests a New Treatment Strategy AID - 10.1124/mol.115.101360 DP - 2016 Feb 01 TA - Molecular Pharmacology PG - 263--272 VI - 89 IP - 2 4099 - http://molpharm.aspetjournals.org/content/89/2/263.short 4100 - http://molpharm.aspetjournals.org/content/89/2/263.full SO - Mol Pharmacol2016 Feb 01; 89 AB - Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist.