Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation
Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation
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SLC31A1的基因多态性通过调节microRNA介导的调节与非小细胞肺癌患者铂类化疗的临床结果相关
DOI：
10.18632/oncotarget.24794
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Wang Haijian
中科院分区：
文献类型：
--
作者：
Sun Chang;Zhang Zhuojun;Qie Jingbo;Wang Yi;Qian Ji;Wang Jiucun;Wu Junjie;Li Qiang;Bai Chunxue;Han Baohui;Gao Zhiqiang;Xu Jibin;Lu Daru;Jin Li;Wang Haijian
SLC31A1是铂类药物摄取的主要转运体，其表达与药物处置和反应密切相关。在1004例接受铂类药物化疗的中国非小细胞肺癌患者中，我们研究了SLC31A1基因多态性与临床结果的关系。Rs10759637杂合子与严重的血小板减少(优势比OR：2.69；P=0.012)和较短的总生存期(风险比[HR]：1.24；P=0.005)有关。Rs2233914纯合子变异与总生存期延长相关(危险比[HR]：0.73；P=0.008)。这些连锁SNP的单倍型和双倍型与血液学毒性相关。在分层分析中，rs10759637和rs2233914与特定亚组(如男性、吸烟者、58岁以上患者、ECOG PS 0-1或鳞癌患者)的总存活率一致相关。Rs10759637可改变hsa-miR-29结合位点的3‘非编码区的局部结构，将其导入16HBE细胞可显著抑制基因表达。Rs10759637突变与报告实验中荧光素酶活性降低和肿瘤组织中SLC31A1转录本表达降低显著相关。因此，这项研究确定了SLC31A1功能多态，它调节miRNA-3‘非编码区相互作用和基因表达，是预测非小细胞肺癌患者铂类化疗临床疗效的潜在药物遗传学生物标记物。
SLC31A1 is the major transporter for platinum drug intake, its expression correlates with drug disposition and response. In 1004 Chinese NSCLC patients with platinum-based chemotherapy, we investigated the association between SLC31A1 polymorphisms and clinical outcomes. Heterozygotes of rs10759637 at 3′UTR was associated with severe thrombocytopenia (odds ratio [OR]: 2.69; P = 0.012) and shorter overall survival (hazard ratio [HR]: 1.24; P = 0.005). Variant homozygote of rs2233914 was correlated with longer overall survival (hazard ratio [HR]: 0.73; P = 0.008). Haplotype and diplotype of these linked SNPs were associated with hematologic toxicities. In stratification analyses, rs10759637 and rs2233914 consistently correlated with overall survival in specific subgroups such as men, smoker, patients older than 58 years, or with ECOG PS 0-1, or with squamous cell carcinoma. rs10759637 could change the local structure of 3′UTR harboring putative binding sites for hsa-miR-29, whose transfection into 16HBE cells resulted in remarkable suppression of gene expression. The rs10759637 variant significantly correlated with lowered luciferase activity in reporter assays and decreased expression of SLC31A1 transcript in tumorous tissues. The study thereby identified functional polymorphism of SLC31A1 that modulates miRNA-3′UTR interaction and gene expression as potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.
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影响因子：
5.3
作者：
Chen, Helen H. W.;Yan, Jiang-Jou;Chen, Wen-Chung;Kuo, Macus Tien;Lai, Yu-Hsuan;Lai, Wu-Wei;Liu, Hsiao-Sheng;Su, Wu-Chou
通讯作者：
Su, Wu-Chou
影响因子：
5.3
作者：
Enciso, Maria;Sarasa, Jonas;Wells, Dagan
通讯作者：
Wells, Dagan
DOI：
10.1093/oxfordjournals.annonc.a058384
发表时间：
1993-12
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Mcvie Jg
通讯作者：
Mcvie Jg
DOI：
10.1165/rcmb.2010-0323oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Cushing, Leah;Kuang, Ping Ping;Lue, Jining
通讯作者：
Lue, Jining
影响因子：
9.8
作者：
Wittke-Thompson, JK;Pluzhnikov, A;Cox, NJ
通讯作者：
Cox, NJ