miR-196a 基因多态性作为早期乳腺癌的预后生物标志物。

Genetic polymorphism of miR-196a as a prognostic biomarker for early breast cancer.

机构信息

Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.

Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea

出版信息

Anticancer Res. 2014 Jun;34(6):2943-9.

PMID:24922658

Abstract

BACKGROUND

As microRNAs (miRNA) may play important roles in tumorigenesis by regulating the expression of proto-oncogenes or tumor suppressor genes, the present study analyzed single nucleotide polymorphisms (SNPs) located in miRNA and miRNA-binding sites of various genes and their impact on prognosis for 452 patients with early breast cancer.

MATERIALS AND METHODS

Three SNPs of miR-196a (rs3746444, rs11614913, and rs1044129) were selected using in silico analysis and genotyped using the Sequenom MassARRAY.

RESULTS

The median age of patients was 48 years, and 283 (62.6%) were estrogen and/or progesterone receptor (ER/PgR)-positive, 86 (19.0 %) had human epidermal growth factor receptor 2 (HER2)-overexpressing, and 77 (17.0%) had triple-negative early breast cancer. During the median follow-up of 6.9 years, 67 (14.8%) relapses and 55 (12.2%) deaths were recorded. Among the three polymorphisms, the C allele of miR-196a rs11614913T>C was significantly associated with worse disease-free (DFS) and distant DFS (DDFS) when adjusted for clinical and pathological parameters. In particular, the prognostic impact of rs11614913 was limited to the hormone receptor-expressing subtype, where the patients bearing the CC genotype showed worse survival in terms of DFS and DDFS compared with the patients with the TT or TC genotype as a recessive model (hazard ratio=2.610, p=0.003 for DFS; hazard ratio=2.730, p=0.013 for DDFS).

CONCLUSION

The current study provides evidence that the miR-196a rs11614913T>C polymorphisms are possible prognostic biomarker for patients with hormone receptor-expressing early breast cancer.

摘要

背景

微小 RNA（miRNA）可能通过调节原癌基因或肿瘤抑制基因的表达在肿瘤发生中发挥重要作用，本研究分析了位于 miRNA 及其靶基因 miRNA 结合位点的单核苷酸多态性（SNP），并探讨其对 452 例早期乳腺癌患者预后的影响。

材料和方法

使用计算机分析选择 miR-196a（rs3746444、rs11614913 和 rs1044129）的三个 SNP，并使用Sequenom MassARRAY 进行基因分型。

结果

患者的中位年龄为 48 岁，283 例（62.6%）为雌激素和/或孕激素受体（ER/PgR）阳性，86 例（19.0%）为人表皮生长因子受体 2（HER2）过表达，77 例（17.0%）为三阴性早期乳腺癌。在中位随访 6.9 年期间，有 67 例（14.8%）复发和 55 例（12.2%）死亡。在这三个多态性中，miR-196a rs11614913T>C 的 C 等位基因与无病生存期（DFS）和远处无病生存期（DDFS）显著相关，在调整临床和病理参数后仍具有统计学意义。特别是，rs11614913 的预后影响仅限于激素受体表达亚型，在隐性模型中，携带 CC 基因型的患者的 DFS 和 DDFS 生存情况均较 TT 或 TC 基因型患者差（DFS 的风险比=2.610，p=0.003；DDFS 的风险比=2.730，p=0.013）。