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Article: Identification of transmembrane protein 98 as a novel chemoresistance-conferring gene in hepatocellular carcinoma

TitleIdentification of transmembrane protein 98 as a novel chemoresistance-conferring gene in hepatocellular carcinoma
Authors
Issue Date2014
Citation
Molecular Cancer Therapeutics, 2014, v. 13 n. 5, p. 1285-1297 How to Cite?
AbstractChemoresistance 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. TMEM98 mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (P < 0.0001). Upregulation of TMEM98 was significantly correlated with advanced tumor stage (P = 0.048), high incidence of early tumor recurrence (P = 0.005), poor overall survival (P = 0.029), and poor disease-free survival (P = 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of TMEM98 mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (P = 0.046). Moreover, patients with poor response to TACE treatment had higher degree of TMEM98 upregulation than the responsive patients. In vitro and in vivo 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. (C) 2014 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/196575
ISSN
2015 Impact Factor: 5.579
2015 SCImago Journal Rankings: 3.224
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorNg, KTPen_US
dc.contributor.authorLo, CMen_US
dc.contributor.authorGuo, DYen_US
dc.contributor.authorQi, Xen_US
dc.contributor.authorLi, Cen_US
dc.contributor.authorGeng, Wen_US
dc.contributor.authorLiu, Xen_US
dc.contributor.authorLing, Cen_US
dc.contributor.authorMa, YYen_US
dc.contributor.authorYeung, WHen_US
dc.contributor.authorShao, Yen_US
dc.contributor.authorPoon, RTPen_US
dc.contributor.authorFan, STen_US
dc.contributor.authorMan, Ken_US
dc.date.accessioned2014-04-22T08:37:59Z-
dc.date.available2014-04-22T08:37:59Z-
dc.date.issued2014en_US
dc.identifier.citationMolecular Cancer Therapeutics, 2014, v. 13 n. 5, p. 1285-1297en_US
dc.identifier.issn1535-7163-
dc.identifier.urihttp://hdl.handle.net/10722/196575-
dc.description.abstractChemoresistance 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. TMEM98 mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (P < 0.0001). Upregulation of TMEM98 was significantly correlated with advanced tumor stage (P = 0.048), high incidence of early tumor recurrence (P = 0.005), poor overall survival (P = 0.029), and poor disease-free survival (P = 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of TMEM98 mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (P = 0.046). Moreover, patients with poor response to TACE treatment had higher degree of TMEM98 upregulation than the responsive patients. In vitro and in vivo 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. (C) 2014 AACR.-
dc.languageengen_US
dc.relation.ispartofMolecular Cancer Therapeuticsen_US
dc.titleIdentification of transmembrane protein 98 as a novel chemoresistance-conferring gene in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailNg, KTP: ledodes@hku.hken_US
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_US
dc.identifier.emailQi, X: qixiang515@connect.hku.hken_US
dc.identifier.emailLi, C: doclicx@hku.hken_US
dc.identifier.emailGeng, W: weigeng@hku.hken_US
dc.identifier.emailLiu, X: liuxb301@hku.hken_US
dc.identifier.emailLing, C: lingccl@hku.hken_US
dc.identifier.emailMa, YY: yyma@hku.hken_US
dc.identifier.emailYeung, WH: why21@hku.hken_US
dc.identifier.emailShao, Y: yshao@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.emailMan, K: kwanman@hku.hken_US
dc.identifier.authorityNg, KTP=rp01720en_US
dc.identifier.authorityLo, CM=rp00412en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.identifier.authorityMan, K=rp00417en_US
dc.identifier.doi10.1158/1535-7163.MCT-13-0806-
dc.identifier.pmid24608572-
dc.identifier.hkuros228551en_US
dc.identifier.volume13en_US
dc.identifier.isiWOS:000335961600022-
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-

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