title: Prediction of in vitro response to interferon-alpha in renal cell carcinoma cell lines.
abstract: We analyzed the correlation between interferon-alpha (IFNalpha) response and gene expression profiles to predict IFNalpha sensitivity and identified key molecules regulating the IFNalpha response in renal cell carcinoma (RCC) cell lines. To classify eight RCC cell lines of the SKRC series into three subgroups according to IFNalpha sensitivity, that is, sensitive, resistant and intermediate group, responses to IFNalpha (300-3000 IU/mL) were quantified by WST-1 assay. Microarray, followed by supervised hierarchical clustering analysis, was applied to selected genes according to IFNalpha sensitivity. In order to find alteration of expression profiles induced by IFNalpha, sequential microarray analyses were performed at 3, 6, and 12 h after IFNalpha treatment of RCC cell lines and mRNA expression level was confirmed using quantitative real time polymerase chain reaction. According to the sequential microarray analysis between IFNalpha-sensitive and -resistant line, seven genes were selected as candidates for IFNalpha-sensitivity-related genes in RCC cell lines. Among these seven genes, we further developed a model to predict tumor inhibition with four genes, that is, adipose differentiation-related protein, microphthalmia associated transcription factor, mitochondrial tumor suppressor 1, and troponin T1 using multiple linear regression analysis (coefficient=0.948, P=0.0291) and validated the model using other RCC cell lines including six primary cultured RCC cells. The expression levels of the combined selected genes may provide predictive information on the IFNalpha response in RCC. Furthermore, the IFNalpha response to RCC might be modulated by regulation of the expression level of these molecules.
authors.affiliation: Department of Urology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. torushim@md.tsukuba.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Shimazui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kojima
authors.forename: Takehiro
authors.initials: T
authors.lastname: Oikawa
authors.forename: Kogenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Honda
authors.forename: Shiro
authors.initials: S
authors.lastname: Hinotsu
authors.forename: Jun
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Kunita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins