Department of Surgery, National University of Ireland, Galway, Ireland.
Ann Surg. 2010 Mar;251(3):499-505. doi: 10.1097/SLA.0b013e3181cc939f.
The development of clinically validated biomarkers for cancer has remained an insurmountable task despite other advances in the field of cancer molecular biology. Mi(cro)RNAs have many characteristics of an ideal biomarker most notably their inherent stability and resilience. Recent blood-based miRNA profiling studies, reporting their presence in serum and plasma, have generated the concept that circulating miRNAs hold much potential as novel noninvasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of circulating microRNAs as novel breast cancer biomarkers.
Using a novel approach to extract miRNAs from the circulation followed by real-time quantitative polymerase chain reaction analysis, levels of a panel of 7 candidate miRNAs were quantified in tissue and blood specimens of 148 patients with breast cancer and 44 age-matched and disease free control individuals.
We report that cancer-specific miRNAs were detected and significantly altered in the circulation of breast cancer patients, and that increased systemic miR-195 levels in breast cancer patients were reflected in breast tumors. Furthermore, we identified that circulating levels of miR-195 and let-7a decreased in cancer patients postoperatively, to levels comparable with control subjects, following curative tumor resection. Finally, we found that specific circulating miRNAs correlated with certain clinicopathological variables, namely nodal status and estrogen receptor status.
These findings suggest that systemic miRNAs have potential use as novel breast cancer biomarkers and may prove useful in clinical management during the perioperative period.
尽管癌症分子生物学领域取得了其他进展,但临床上经过验证的癌症生物标志物的开发仍然是一项艰巨的任务。mi(cro)RNA 具有许多理想生物标志物的特征,尤其是其内在的稳定性和弹性。最近的基于血液的 miRNA 分析研究报告了它们在血清和血浆中的存在,这一概念认为循环 miRNA 具有作为癌症和其他疾病过程新型非侵入性生物标志物的巨大潜力。本研究的目的是研究循环 microRNA 作为新型乳腺癌生物标志物的潜力。
本研究采用一种从循环中提取 miRNA 的新方法,然后进行实时定量聚合酶链反应分析,对 148 例乳腺癌患者和 44 例年龄匹配且无疾病对照组个体的组织和血液标本中的 7 个候选 miRNA 进行定量分析。
我们报告称,在乳腺癌患者的循环中检测到并显著改变了癌症特异性 miRNA,并且乳腺癌患者的系统性 miR-195 水平升高反映在乳腺肿瘤中。此外,我们发现,在接受根治性肿瘤切除术后,癌症患者的循环 miR-195 和 let-7a 水平降低,与对照组相当。最后,我们发现特定的循环 miRNA 与某些临床病理变量(即淋巴结状态和雌激素受体状态)相关。
这些发现表明,系统 miRNA 具有作为新型乳腺癌生物标志物的潜在用途,并且可能在围手术期的临床管理中证明有用。