Preoperative prediction nomogram based on primary tumor miRNAs signature and clinical-related features for axillary lymph node metastasis in early-stage invasive breast cancer
Preoperative prediction nomogram based on primary tumor miRNAs signature and clinical-related features for axillary lymph node metastasis in early-stage invasive breast cancer
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基于原发肿瘤 miRNA 特征和临床相关特征的早期浸润性乳腺癌腋窝淋巴结转移的术前预测列线图
DOI：
10.1002/ijc.31208
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发表时间：
2018-05-01
影响因子：
6.4
通讯作者：
Xie, Xiaoming
中科院分区：
文献类型：
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作者：
Xie, Xinhua;Tan, Weige;Xie, Xiaoming
超过一半接受腋窝淋巴结 (ALN) 手术的早期浸润性乳腺癌 (EIBC) 患者的 ALN 呈阴性。因此，为了避免过度治疗，我们的目标是建立并验证一种新的列线图模型，用于 EIBC 患者术前诊断 ALN 状态。总共有来自两个独立中心的 864 名 EIBC 患者参与了我们的研究。对于发现集，通过微阵列分析发现了在 ALN 转移中具有功能作用的 miRNA 表达谱，并通过定量聚合酶链反应 (PCR) 进行了验证。对于训练和验证队列，我们使用 PCR 来量化模型开发队列中的 miRNA 表达，并评估内部验证队列和外部独立验证队列中的 miRNA 特征。使用多变量逻辑回归分析根据 miRNA 特征和临床变量建立 ALN 转移可能性的列线图模型。九个 miRNA 的特征与 ALN 状态显着相关。我们的列线图包括 miRNA 特征和临床相关变量（年龄、肿瘤大小、肿瘤位置和腋窝超声报告的 ALN 状态），其预测能力显着高于仅考虑临床相关因素的模型（一致性指数：0.856、0.796），并且在两个验证队列中也表现良好（一致性指数：0.841、0.747）。我们的列线图是一种可靠的预测方法，可方便地用于术前预测 EIBC 患者的 ALN 状态。因此，经过前瞻性多中心临床试验的进一步证实，未来对于部分 EIBC 患者省略腋窝手术可能是可行的。最新消息？腋窝淋巴结 (ALN) 受累的手术分期可为乳腺癌的临床治疗决策提供依据。然而，对于早期疾病患者，腋窝手术分期可能会产生持久的副作用，包括手臂麻木和肩部运动障碍。在此，开发了一种包含与 ALN 转移相关的 miRNA 特征的列线图模型，用于预测早期浸润性乳腺癌患者的 ALN 状态。将 miRNA 特征与临床相关危险因素相结合，成功预测术前 ALN 状态。在识别 ALN 转移风险极低的患者时，该新模型有可能促进治疗优化并有助于防止不必要的手术。
More than half patients who undergo axillary lymph node (ALN) surgery are ALN negative in early-stage invasive breast cancer (EIBC). Thus, to avoid excessive treatment, we aim to establish and validate a novel nomogram model for the preoperative diagnosis of ALN status in patients with EIBC. In total, 864 patients with EIBC from two independent centers were enrolled in our study. For the discovery set, miRNAs expression profiling with functional roles in ALN metastasis was discovered by microarray analysis and validated by quantitative polymerase chain reaction (PCR). For the training and validation cohorts, we used PCR to quantify miRNAs expression in a model development cohort and assessed miRNAs signature in an internal validation cohort and external independent validation cohort. Multivariable logistic regression analyses were used to establish a nomogram model for the likelihood of ALN metastasis from miRNAs signature and clinical variables. A signature of nine-miRNA was significantly associated with ALN status. The predictive ability of our nomogram that included miRNAs signature and clinical-related variables (age, tumor size, tumor location and axillary ultrasound-reported ALN status) was significantly greater than a model that only considered clinical-related factors (concordance index: 0.856, 0.796) and also performed well in the two validation cohorts (concordance index: 0.841, 0.747). Our nomogram is a reliable prediction method that can be conveniently used to preoperatively predict ALN status in patients with EIBC. Therefore, after further confirmation in prospective and multicenter clinical trial, omission of axillary surgery may be feasible for some patients with EIBC in the future.What's new?Surgical staging of axillary lymph node (ALN) involvement informs decisions regarding the clinical management of breast cancer. In patients with early-stage disease, however, surgical staging of the axilla can have lasting adverse effects, including arm numbness and shoulder motion impairment. Here, a nomogram model incorporating miRNA signatures relevant to ALN metastasis was developed to predict ALN status in patients with early-stage invasive breast cancer. Combining miRNA signatures with clinically relevant risk factors successfully predicted ALN status preoperatively. In identifying patients with very low risk of ALN metastasis, the novel model can potentially facilitate treatment optimization and help prevent unnecessary procedures.