PARP1 特异性多态性和单倍型与非小细胞肺癌亚型的关联。
Association of PARP1-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes.
机构信息
Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Department of Health Behavior and Health Education, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
出版信息
PLoS One. 2020 Dec 7;15(12):e0243509. doi: 10.1371/journal.pone.0243509. eCollection 2020.
OBJECTIVE
The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer.
MATERIALS AND METHODS
DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed.
RESULTS
SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001.
CONCLUSION
PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.
目的
PARP1 在肺癌中的致癌作用尚不清楚。等位基因水平的分析不能完全解释 PARP1 对肺癌的作用。我们的研究旨在进一步探讨 PARP1 单倍型与肺癌之间的关系。
材料和方法
从非小细胞肺癌（NSCLC）肿瘤和相邻正常新鲜冷冻组织中提取 DNA 和 RNA。对 5 个 PARP1-SNPs 进行基因分型，并使用 IMPUTE 和 SHAPEIT 软件对 PARP1 特异性 SNPs 进行推断。对 SNPs 进行等位基因、单倍型和 SNP-SNP 相互作用分析。分析了 SNPs 与 mRNA/蛋白表达的相关性。
结果
SNP 推断增加了未基因分型 SNPs 的关联分析能力。与正常组织相比，肿瘤组织样本更可能携带 rs1805414（OR=1.85；95%CI：1.12-3.06；P 值：0.017）和 rs1805404（OR=2.74；95%CI 1.19-6.32；P 值：0.015）。我们的研究首次表明，PARP1 上包含 5 个 SNPs 的单倍型（rs1136410、rs3219073、rs1805414、rs1805404、rs1805415）能够区分 NSCLC 肿瘤与正常组织。rs3219073、rs1805415 和 rs1805414 之间的相互作用与 NSCLC 肿瘤显著相关，OR 范围为 3.61-6.75；95%CI 为 1.82 至 19.9；P 值<0.001。
结论
与单个等位基因相比，PARP1 单倍型可能是肺癌发生和预后的更好预测因子。
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