Qian Biyun, Katsaros Dionyssios, Lu Lingeng, Preti Mario, Durando Antonio, Arisio Riccardo, Mu Lina, Yu Herbert
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Breast Cancer Res Treat. 2009 Sep;117(1):131-40. doi: 10.1007/s10549-008-0219-7. Epub 2008 Oct 19.
MicroRNA-21 (miR-21) is considered an onco-microRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-beta) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-beta, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-beta1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-beta may up-regulate its expression.
微小RNA-21（miR-21）因其能够抑制多种肿瘤抑制基因的作用并促进肿瘤细胞生长、侵袭和转移，而被视为一种致癌微小RNA。最近，发现转化生长因子-β（TGF-β）可上调miR-21的表达，且miR-21表达升高在乳腺癌中较为常见。为了评估miR-21对疾病进展的影响及其与TGF-β的关联，我们分析了乳腺癌中miR-21的表达情况。在手术过程中从344例诊断为原发性乳腺癌的患者中收集新鲜肿瘤样本。使用TaqMan微小RNA检测法以U6作为参照来测量肿瘤样本中miR-21的表达。比较了不同疾病分期、肿瘤分级、组织学类型、激素受体状态和淋巴结受累情况的miR-21表达水平。进行Cox比例风险回归分析以评估miR-21表达与无病生存期和总生存期的关联。研究结果表明，在所有肿瘤样本中均检测到miR-21的表达，且存在很大差异。miR-21高表达与侵袭性疾病特征相关，包括高肿瘤分级、激素受体阴性状态和导管癌。高miR-21也与TGF-β1呈正相关。在所有患者中未发现患者生存期与miR-21表达之间存在关联，但尽管对预后无价值，高miR-21与早期患者较差的无病生存期相关（风险比=2.08，95%置信区间：1.08 - 4.00）。该研究支持miR-21是乳腺癌致癌微小RNA这一观点。miR-21表达升高可能促进肿瘤进展，且TGF-β可能上调其表达。
