Data from Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Abstract

<div>Abstract<p>Chemoresistance is one of the major obstacles in systemic chemotherapy and targeted therapy for patients with advanced hepatocellular carcinoma. To identify novel chemoresistance-associated targets in hepatocellular carcinoma, chemoresistant hepatocellular carcinoma cell lines were established. By comparing the global gene expression profiles between chemoresistant and chemosensitive cell lines, eight novel chemoresistance-associated genes were identified to be significantly associated with the commonly augmented chemoresistance of hepatocellular carcinoma cells. One upregulated candidate named transmembrane protein 98 (TMEM98) was found to be overexpressed in 80 of 118 (67.80%) of patients with hepatocellular carcinoma. <i>TMEM98</i> mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (<i>P</i> < 0.0001). Upregulation of <i>TMEM98</i> was significantly correlated with advanced tumor stage (<i>P</i> = 0.048), high incidence of early tumor recurrence (<i>P</i> = 0.005), poor overall survival (<i>P</i> = 0.029), and poor disease-free survival (<i>P</i> = 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of <i>TMEM98</i> mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (<i>P</i> = 0.046). Moreover, patients with poor response to TACE treatment had higher degree of <i>TMEM98</i> upregulation than the responsive patients. <i>In vitro</i> and <i>in vivo</i> studies showed that suppression of TMEM98 in chemoresistant hepatocellular carcinoma cells restored their chemosensitivity, while forced overexpression of TMEM98 enhanced their chemoresistance. The mechanism of TMEM98 in conferring chemoresistance of hepatocellular carcinoma might be possibly through activation of the AKT pathway and deactivation of p53. In conclusion, we identified a panel of novel common chemoresistance-associated genes and demonstrated that TMEM98 is a chemoresistance-conferring gene in hepatocellular carcinoma. <i>Mol Cancer Ther; 13(5); 1285–97. ©2014 AACR</i>.</p></div>