Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data.
Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data.
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DOI：
10.3892/ijo.28.5.1153
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发表时间：
2006-05
影响因子：
5.2
通讯作者：
Tatsushi Shimokuni;K. Tanimoto;K. Hiyama;K. Otani;M. Ohtaki;J. Hihara;Kazuhiro Yoshida;T. Noguchi;K. Kawahara;S. Natsugoe;T. Aikou;Y. Okazaki;Y. Hayashizaki;Yuji Sato;S. Todo;E. Hiyama;M. Nishiyama
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文献类型：
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作者：
Tatsushi Shimokuni;K. Tanimoto;K. Hiyama;K. Otani;M. Ohtaki;J. Hihara;Kazuhiro Yoshida;T. Noguchi;K. Kawahara;S. Natsugoe;T. Aikou;Y. Okazaki;Y. Hayashizaki;Yuji Sato;S. Todo;E. Hiyama;M. Nishiyama
食道癌是一种高度致命的疾病，最佳治疗方法尚不清楚。由于辅助化疗提供了更好的生存机会，我们试图开发一种化疗敏感性预测模型来提高个体对治疗的反应。通过对20个KYSE鳞癌细胞系中8种药物的综合基因表达分析(cDNA微阵列和寡核苷酸芯片)和四甲基偶氮唑盐比色法，筛选其表达水平与细胞药物敏感性相关的候选标记基因。经实时荧光定量RT-PCR验证后，我们进行多元回归分析，利用所选标记基因的量化表达数据建立药物敏感性预测公式。使用相同的一组基因，我们还构建了18例患者对5-FU为主的化疗的个体临床反应的预测模型。我们选择了5个较好的标记基因，称为药物敏感性决定因素，确定了8种抗癌药物[5-FU，CDDP，DOX和CPT-11(SN-38)]中4种新的预测基因，并从总体和无病生存的角度开发了对这4种药物的体外敏感性和5-FU辅助化疗的临床疗效的高度预测公式。我们选择的基因很可能是有效的药物敏感性标记，使用这9个新基因的公式将在预测方面提供优势。
Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drug-sensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.