Prediction of in vitro response to interferon-alpha in renal cell carcinoma cell lines.
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.
Shimazui
Toru
T
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
Ami
Yoshihiro
Y
Yoshikawa
Kazuhiro
K
Uchida
Kazuhiko
K
Kojima
Takahiro
T
Oikawa
Takehiro
T
Nakamura
Kogenta
K
Honda
Nobuaki
N
Hinotsu
Shiro
S
Miyazaki
Jun
J
Kunita
Noriko
N
Akaza
Hideyuki
H
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
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins