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miRNA 结合位点内的 SNPs 与乳腺癌的预后。

SNPs within microRNA binding sites and the prognosis of breast cancer.

机构信息

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China.

Department of Infection Control, Tianjin Huanhu Hospital, Tianjin 300350, People's Republic of China.

出版信息

Aging (Albany NY). 2021 Feb 26;13(5):7465-7480. doi: 10.18632/aging.202612.

Abstract

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (<0.05), and only rs10878441 was statistically significant in stage II (AA vs CC, HR=2.21, 95% CI: 1.11-4.42, =0.024). We combined the data from stage I and stage II, and found that, compared with rs10878441 AA genotype, CC genotype was associated with poor survival of breast cancer (HR=2.19, 95% CI: 1.30-3.70, =0.003). Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II and lymph node-negative patients (<0.05). The Leucine-rich repeat kinase 2 (LRRK2) rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population and may be used as a potential prognostic biomarker for breast cancer. • The LRRK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population. • Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients.

摘要

单核苷酸多态性(SNP)位于 microRNA 结合位点内,可以影响 microRNA 与 mRNA 的结合,并调节基因表达,从而影响癌症的预后。在这里,我们对 2647 例乳腺癌患者进行了两阶段研究,以探讨 microRNA 结合位点内的 SNP 与乳腺癌预后之间的关系。在第一阶段,我们使用 Illumina Goldengate 平台对 microRNA 结合位点内的 192 个 SNP 进行了基因分型。在第二阶段,我们使用 TaqMan 平台在另一个数据集验证了与乳腺癌预后相关的 SNP。在第一阶段,我们确定了 8 个与乳腺癌预后显著相关的 SNP(<0.05),只有 rs10878441 在第二阶段具有统计学意义(AA 与 CC,HR=2.21,95%CI:1.11-4.42,=0.024)。我们结合了第一阶段和第二阶段的数据,发现与 rs10878441 AA 基因型相比,CC 基因型与乳腺癌的不良生存相关(HR=2.19,95%CI:1.30-3.70,=0.003)。分层分析表明,rs10878441 与 II 级和淋巴结阴性患者的乳腺癌预后相关(<0.05)。LRRK2 rs10878441 CC 基因型与中国人群乳腺癌的不良预后相关,可能作为乳腺癌的潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/906b/7993692/2b4359005b4e/aging-13-202612-g001.jpg

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