Dan Shingo, Shirakawa Mieko, Mukai Yumiko, Yoshida Yoko, Yamazaki Kanami, Kawaguchi Tokuichi, Matsuura Masaaki, Nakamura Yusuke, Yamori Takao
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455.
Cancer Sci. 2003 Dec;94(12):1074-82. doi: 10.1111/j.1349-7006.2003.tb01403.x.
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.
我们之前研究了9216个基因的表达与39种人类癌细胞系的各种化学敏感性之间的相关性(1),发现AKR1B1和CTSH的表达水平分别与对多种药物的敏感性和耐药性相关。为了验证这些相关性,我们研究了这两个基因在另外12种胃癌细胞系中的表达以及化学敏感性。在另外的细胞系中,AKR1B1的表达与所检测的23种药物中的8种的敏感性显著相关,而CTSH的表达仅与所检测的27种药物中的一种(MS-247)呈显著负相关。它们的表达分别与其余药物的敏感性和耐药性弱相关。此外,当将这12种细胞系分为高表达组和低表达组时,使用曼-惠特尼U检验对这些组进行比较发现,AKR1B1和CTSH的高表达水平分别与21种药物的敏感性和8种药物的耐药性相关。目前的结果表明,AKR1B1和CTSH可能是预测对某些药物敏感性的良好标志物,并且我们的39种细胞系组合有潜力识别候选预测标志物基因。