MicroRNA-9 as potential biomarker for breast cancer local recurrence and tumor estrogen receptor status.
MicroRNA-9 as potential biomarker for breast cancer local recurrence and tumor estrogen receptor status.
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DOI：
10.1371/journal.pone.0039011
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zheng YL
中科院分区：
文献类型：
--
作者：
Zhou X;Marian C;Makambi KH;Kosti O;Kallakury BV;Loffredo CA;Zheng YL
MicroRNA (miR) 是参与许多细胞功能的小型非蛋白质编码转录物。许多 miR 已成为重要的癌症生物标志物。在本研究中，我们研究了乳腺肿瘤中的 miR 水平是否可以预测乳腺癌局部复发 (LR)。这项研究包括 68 名在隆巴迪综合癌症中心被诊断患有乳腺癌的女性。患有 LR 的乳腺癌患者和不患有 LR 的乳腺癌患者在手术年份、诊断时年龄和手术类型上进行匹配。通过使用 miR 阵列筛选来自 8 个 LR 病例和 8 个无 LR 病例的 16 个乳腺肿瘤样本中的 754 个人类 miR 的表达水平，鉴定了候选 miR。使用实时 PCR 在 52 个肿瘤样本中进一步验证了 8 个候选 miR，它们在有 LR 和无 LR 的肿瘤之间显示出显着差异。在所有病例以及雌激素受体 (ER) 阳性病例亚组中，miR-9 的较高表达与乳腺癌 LR 显着相关 (p = 0.02)。所有肿瘤和 ER 阳性肿瘤的 miR-9 受试者工作特征 (ROC) 曲线的 AUC（曲线下面积）分别为 0.68 (p = 0.02) 和 0.69 (p = 0.02)。在 ER 阳性病例中，Kaplan-Meier 分析显示，miR-9 水平较低的患者的 10 年无 LR 生存率显着更高（67.9% vs 30.8%，p = 0.02）。 miR-9 和另一种 miR 候选物 miR-375 的表达水平也与 ER 状态密切相关（两者 p<0.001）。 miR-9 作为 LR 生物标志物的潜力值得用更大的样本量进行进一步研究。
MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions. Many miRs have emerged as important cancer biomarkers. In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR). Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study. Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery. Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR. Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR. Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02). The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 0.68 (p = 0.02) and 0.69 (p = 0.02), respectively. In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (67.9% vs 30.8%, p = 0.02). Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0.001 for both). The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size.