A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer

被引：13

作者：

Hong, Mi Jeong ^{[1
,2
,3
]}

Lee, Shin Yup ^{[4
,5
]}

Choi, Jin Eun ^{[1
,2
,3
]}

Jin, Cheng Cheng ^{[1
,2
]}

Kang, Hyo Jung ^{[1
,2
]}

Baek, Sun Ah ^{[1
,2
]}

Lee, So Yeon ^{[5
]}

Shin, Kyung Min ^{[6
]}

Jeong, Ji Yun ^{[7
]}

Lee, Won Kee ^{[8
]}

Yoo, Seung Soo ^{[4
,5
]}

Lee, Jaehee ^{[4
]}

Cha, Seung Ick ^{[4
]}

Kim, Chang Ho ^{[4
]}

Son, Ji Woong ^{[9
]}

Park, Jae Yong ^{[1
,2
,3
,4
,5
]}

机构：

[1] Kyungpook Natl Univ, Med Ctr, Dept Biochem, Daegu, South Korea

[2] Kyungpook Natl Univ, Med Ctr, Dept Cell Biol, Daegu, South Korea

[3] Kyungpook Natl Univ, Med Ctr, Cell & Matrix Res Inst, Daegu, South Korea

[4] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Daegu, South Korea

[5] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu, South Korea

[6] Kyungpook Natl Univ, Med Ctr, Dept Radiol, Daegu, South Korea

[7] Kyungpook Natl Univ, Med Ctr, Dept Pathol, Daegu, South Korea

[8] Kyungpook Natl Univ, Sch Med, Biostat Ctr, Daegu, South Korea

[9] Konyang Univ Hosp, Dept Internal Med, Daejeon, South Korea

来源：

ONCOTARGET | 2016年 / 7卷 / 13期

基金：

新加坡国家研究基金会;

关键词：

non-small cell lung cancer; miRNA target sites; polymorphisms; chemotherapy; response; DNA-REPAIR; BREAST-CANCER; BINDING-SITES; POLYMORPHISMS; EXPRESSION; RISK; THERAPY; TUMORS; INHIBITION; MECHANISMS;

D O I：

10.18632/oncotarget.7433

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites with the clinical outcomes of first line paclitaxel-cisplatin chemotherapy in advanced NSCLC. Eighty SNPs in miRNA binding sites of cancer related genes selected from 18,500 miRNA: target bindings in crosslinking, ligation, and sequencing of hybrids (CLASH) data were investigated in 379 advanced NSCLC patients using a sequenom mass spectrometry-based genotype assay. qRT-PCR and luciferase assay were conducted to examine functional relevance of potentially functional SNPs in miRNA binding sites. Of the 80 SNPs analyzed, 16 SNPs were significantly associated with the clinical outcomes after chemotherapy. Among these, ANAPC1 rs3814026C>T, ETS2 rs461155A>G, SORBS1 rs7081076C>A and POLR2A rs2071504C>T could predict both chemotherapy response and survival. Notably, ETS2 rs461155A>G was significantly associated with decreased ETS2 mRNA expression in both tumor and paired normal lung tissues (Ptrend = 4 x 10(-7), and 3 x 10(-4), respectively). Consistently, a decreased expression of the reporter gene for the G allele of rs461155 compared with the A allele was observed by luciferase assay. These findings suggest that the four SNPs, especially ETS2 rs461155A>G, could be used as biomarkers predicting the clinical outcomes of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.

引用

页码：15948 / 15958

页数：11

共 40 条

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