Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, United States of America.
PLoS One. 2011;6(12):e28650. doi: 10.1371/journal.pone.0028650. Epub 2011 Dec 13.
Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.
Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.
Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.
These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
癌症分期和治疗假设分为局限性或转移性疾病。我们提出了一种中间状态,定义为≤ 5 个累积转移灶,称为寡转移。与广泛的多转移相比,寡转移患者可能受益于针对转移的局部治疗。然而,许多最初表现为寡转移的患者进展为多转移。进展的预测因素可以改善对转移导向治疗的患者选择。
在这里,我们确定了接受高剂量放疗的寡转移患者肿瘤样本中 microRNA 表达的模式。
未能发展为多转移的患者具有独特的微 RNA 分类器特征,其中包括 microRNA-200 家族。我们创建了一个寡转移-多转移异种移植模型,其中患者来源的 microRNA 可区分两种转移结果。寡转移细胞系中 microRNA-200c 的增强导致多转移进展。
这些结果表明寡转移具有生物学基础,并且有可能使用 microRNA 表达来识别在针对转移的治疗后最有可能保持寡转移的患者。