Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
PLoS One. 2012;7(6):e39011. doi: 10.1371/journal.pone.0039011. Epub 2012 Jun 18.
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.
微小 RNA（miRs）是参与许多细胞功能的小非编码转录物。许多 miRs 已成为重要的癌症生物标志物。在本研究中，我们研究了乳腺癌肿瘤中的 miR 水平是否可预测乳腺癌局部复发（LR）。本研究纳入了在 Lombardi 综合癌症中心诊断为乳腺癌的 68 名女性患者。LR 患者和无 LR 患者根据手术年份、诊断时的年龄和手术类型进行匹配。通过在 8 例有 LR 的病例和 8 例无 LR 的病例的 16 例乳腺癌肿瘤样本中使用 miR 阵列筛选 754 个人类 miR 的表达水平，鉴定候选 miR。使用实时 PCR 在 52 个肿瘤样本中进一步验证了在有 LR 和无 LR 的肿瘤之间显示出显著差异的 8 个候选 miR。miR-9 的高表达与所有病例以及雌激素受体（ER）阳性病例的乳腺癌 LR 显著相关（p = 0.02）。miR-9 的 ROC 曲线下面积（AUC）对于所有肿瘤和 ER 阳性肿瘤分别为 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 10 年无 LR 生存显著更好（67.9% vs 30.8%，p = 0.02）。miR-9 和另一个 miR 候选物 miR-375 的表达水平也与 ER 状态密切相关（p<0.001）。miR-9 作为 LR 生物标志物的潜力需要进一步研究，以增加样本量。
