Identification of candidate predictive markers of anticancer drug sensitivity using a panel of human cancer cell lines.
We previously investigated the correlations between the expression of 9216 genes and various chemosensitivities in a panel of 39 human cancer cell lines(1)) and found that the expression levels of AKR1B1 and CTSH were correlated with sensitivity and resistance to multiple drugs, respectively. To validate these correlations, we investigated the expression of these two genes and the chemosensitivities in 12 additional gastric cancer cell lines. The expression of AKR1B1 in the additional cell lines exhibited significant correlations with sensitivities to 8 of the 23 drugs examined, while that of CTSH displayed a significant negative correlation with only one (MS-247) of the 27 drugs examined. Their expressions were weakly correlated with sensitivity and resistance, respectively, to the remainder of the drugs. Moreover, when the 12 cell lines were divided into high-expressing and low-expressing groups, a comparison of these groups using Mann-Whitney's U test revealed that high expression levels of AKR1B1 and CTSH were related to sensitivity to 21 of the drugs and resistance to 8 of the drugs, respectively. The present results suggest that AKR1B1 and CTSH may be good markers for prediction of sensitivity to certain drugs and that our panel of 39 cell lines has the potential to identify candidate predictive marker genes.
Dan
Shingo
S
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455.
Shirakawa
Mieko
M
Mukai
Yumiko
Y
Yoshida
Yoko
Y
Yamazaki
Kanami
K
Kawaguchi
Tokuichi
T
Matsuura
Masaaki
M
Nakamura
Yusuke
Y
Yamori
Takao
T
D000368:Aged; D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000970:Antineoplastic Agents / Q000494:pharmacology; D056655:Cathepsin H; D002403:Cathepsins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H