Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy.
Irinotecan induces small ubiquitin-like modifier (SUMO)-1 conjugation to topoisomerase-I, 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.
National Cancer Center, Research Institute and Hospital, Goyang-si, Gyeonggi-do, Republic of Korea. jymama@ncc.re.kr
Ji-Youn
JY
Han
Geon Kook
GK
Lee
Sun Young
SY
Yoo
Sung Jin
SJ
Yoon
Eun Young
EY
Cho
Heung Tae
HT
Kim
Jin Soo
JS
Lee
D000328:Adult; D000368:Aged; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025842:SUMO-1 Protein / Q000235:genetics*; D016019:Survival Analysis; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D015854:Up-Regulation; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D000077146:Irinotecan; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D002166:Camptothecin