Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy
Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy
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DOI：
10.1038/tpj.2009.46
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发表时间：
2010-04-01
影响因子：
2.8
通讯作者：
Lee, Jin Soo
中科院分区：
文献类型：
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作者：
Han, Ji-Youn;Lee, Geon Kook;Lee, Jin Soo
伊立替康诱导小泛素样修饰物(SUMO)-1与拓扑异构酶-1偶联，从而增强对伊立替康的敏感性。在这项研究中，我们对147例接受伊立替康化疗的非小细胞肺癌（NSCLC）患者的SUMO1和UBC9多态性进行了基因分型，以探讨基因型与肿瘤反应率之间的关系。在42个肿瘤样本中进行了SUMO1和UBC9的免疫组化，并与基因型相关。UBC9 10920CG基因型的应答率显著高于C/C基因型（81% vs 37%, P = 0.0002）。在多变量分析中也发现了这种对肿瘤反应的预测作用（优势比= 8.5,P = 0.003）。此外，与CC基因型相比，UBC9 10920CG基因型引起的肿瘤与更高的SUMO1过表达发生率相关（78% vs 31%, P = 0.021）。这一发现表明，UBC9 10920CG基因型通过上调肿瘤细胞中SUMO1的表达，增强了晚期NSCLC患者对伊立替康化疗的敏感性。
Irinotecan induces small ubiquitin-like modifier (SUMO)-1 conjugation to topoisomerase-1, leading to enhanced sensitivity to irinotecan. In this study, we genotyped SUMO1 and UBC9 polymorphisms in 147 non-small-cell lung cancer (NSCLC) treated with irinotecan chemotherapy to investigate the association between genotypes and tumor response rate. Immunohistochemistry for SUMO1 and UBC9 was performed in 42 tumor samples and correlated with genotypes. The UBC9 10920CG genotype was associated with significantly higher response rate than the C/C genotype (81 vs 37%, P = 0.0002). This predictive effect on tumor response was also seen in multivariate analysis (odds ratio = 8.5, P = 0.003). Moreover, tumors arising from the UBC9 10920CG genotype were associated with higher prevalence of SUMO1 overexpression compared with those with CC genotype (78 vs 31%, P = 0.021). This finding suggests that the UBC9 10920CG genotype enhances sensitivity to irinotecan chemotherapy in advanced NSCLC through upregulation of SUMO1 in tumor cells.