Kim Seok-Hyun, Kim Moon Jin, Cho Yu Ji, Jeong Yi Yeong, Kim Ho-Cheol, Lee Jong Duk, Hwang Young Sil, Kim In-Suk, Lee Suee, Oh Sung Yong, Ling Hui, Lee Gyeong-Won
*Department of Internal Medicine, Division of Hematology and Medical Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon †Department of Internal Medicine, Division of Hematology-Oncology, Gyeongsang National University School of Medicine ‡Department of Internal Medicine, Division of Pulmonology, Gyeongsang National University Hospital, Jinju §Department of Laboratory Medicine, Pusan National University School of Medicine, Busan ∥Department of Internal Medicine, Division of Hematology-Oncology, Dong-A University Medical Center, Busan, Republic of Korea ¶Department of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, TX.
Am J Clin Oncol. 2015 Jun;38(3):294-9. doi: 10.1097/COC.0b013e318297f333.
The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy.
We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model.
The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014).
Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.
ATP结合盒（ABC）转运蛋白ABCG2参与癌细胞的多药耐药（MDR），在耐药中起重要作用。在许多与MDR相关的ABC基因中已鉴定出单核苷酸多态性（SNP），这些SNP似乎通过多种机制影响药物敏感性/耐药性。因此，我们研究了ABCG2单倍型标签SNP（htSNP）是否与接受一线铂类化疗的不可切除非小细胞肺癌（NSCLC）患者的临床结局相关。
我们对129例接受一线铂类化疗的不可切除NSCLC患者的4个ABCG2 htSNP进行了基因分型。使用χ检验（卡方检验）、Kaplan-Meier法和Cox比例风险模型，根据每个ABCG2 htSNP分析患者的临床特征、治疗结局以及htSNP在患者对铂类化疗的反应、生存和不良事件方面的预测价值。
rs2725264与总生存期（OS）显著相关（P = 0.018，对数秩检验）。rs2725264基因型为T/T、T/C和C/C的患者的中位生存期（月）分别为35.75（95%置信区间[CI]，24.25 - 47.25）、34.25（风险比[HR] 1.27 [0.68至2.35]；95% CI，27.16 - 41.34）和14.89（HR 3.22 [1.26至8.24]，95% CI，13.86 - 15.92）。通过Cox比例风险模型分析，rs2725264被确定为独立因素（P = 0.028）。在紫杉烷类组中，OS与rs2725264相关（P = 0.041），而在吉西他滨组中，OS与rs4148149相关（P = 0.014）。
我们的数据表明，ABCG2 htSNP rs（2725264（总体组和紫杉烷 - 铂联合组）和rs4148149（吉西他滨 - 铂联合组）与接受一线铂类化疗的不可切除NSCLC患者的OS相关。因此，ABCG2 htSNP rs2725264可能与接受一线铂类化疗的不可切除NSCLC患者的OS独立相关。
