Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA.
J Transl Med. 2012 Aug 2;10:155. doi: 10.1186/1479-5876-10-155.
Identification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions. We hypothesized that serum microRNAs (miRNAs) could provide prognostic information at the time of diagnosis unaccounted for by the current staging system and could be useful in detecting recurrence after resection.
We screened 355 miRNAs in sera from 80 melanoma patients at primary diagnosis (discovery cohort) using a unique quantitative reverse transcription-PCR (qRT-PCR) panel. Cox proportional hazard models and Kaplan-Meier recurrence-free survival (RFS) curves were used to identify a miRNA signature with prognostic potential adjusting for stage. We then tested the miRNA signature in an independent cohort of 50 primary melanoma patients (validation cohort). Logistic regression analysis was performed to determine if the miRNA signature can determine risk of recurrence in both cohorts. Selected miRNAs were measured longitudinally in subsets of patients pre-/post-operatively and pre-/post-recurrence.
A signature of 5 miRNAs successfully classified melanoma patients into high and low recurrence risk groups with significant separation of RFS in both discovery and validation cohorts (p = 0.0036, p = 0.0093, respectively). Significant separation of RFS was maintained when a logistic model containing the same signature set was used to predict recurrence risk in both discovery and validation cohorts (p < 0.0001, p = 0.033, respectively). Longitudinal expression of 4 miRNAs in a subset of patients was dynamic, suggesting miRNAs can be associated with tumor burden.
Our data demonstrate that serum miRNAs can improve accuracy in identifying primary melanoma patients with high recurrence risk and in monitoring melanoma tumor burden over time.
识别具有高复发风险的黑色素瘤患者并对其进行监测对于做出明智的管理决策至关重要。我们假设血清 microRNAs（miRNAs）可以提供当前分期系统无法解释的诊断时的预后信息，并且可以用于检测切除后的复发。
我们使用独特的定量逆转录-PCR（qRT-PCR）面板筛选了 80 名原发性黑色素瘤患者（发现队列）的 355 种 miRNA。使用 Cox 比例风险模型和 Kaplan-Meier 无复发生存（RFS）曲线来识别具有预后潜力的 miRNA 特征，该特征可调整分期。然后，我们在另一组 50 名原发性黑色素瘤患者（验证队列）中测试了 miRNA 特征。进行逻辑回归分析以确定 miRNA 特征是否可以确定两个队列中复发的风险。对术前和术后以及复发前和复发后的部分患者进行了选定 miRNA 的纵向测量。
5 个 miRNA 的特征成功地将黑色素瘤患者分为高复发风险和低复发风险组，在发现队列和验证队列中 RFS 均有明显分离（p = 0.0036，p = 0.0093）。当使用包含相同特征集的逻辑模型来预测发现队列和验证队列中的复发风险时，RFS 的分离仍保持显著（p < 0.0001，p = 0.033）。在一组患者中，4 个 miRNA 的纵向表达是动态的，这表明 miRNA 可以与肿瘤负担相关。
我们的数据表明，血清 miRNAs 可以提高识别高复发风险的原发性黑色素瘤患者的准确性，并可以随时间监测黑色素瘤肿瘤负担。
