前哨淋巴结活检是临床判断可手术三阴性乳腺癌腋窝淋巴结转移的标准手术分期方法。对于乳腺癌淋巴结转移的非手术预测，目前主要依靠临床病理特征，但是并不可靠，尤其对于三阴性乳腺癌这种高度异质性疾病。
2018年8月6日，美国转化肿瘤学会官方期刊《肿瘤学家》在线发表复旦大学附属肿瘤医院胡欣和邵志敏、中国科学院上海生命科学研究院王鹏等学者的研究报告，建立了一种预测三阴性乳腺癌患者腋窝淋巴结转移的模型，以避免不必要的腋窝分期手术。
该研究根据美国国家生物技术信息中心（NCBI）基因表达大棚车（GEO）数据库的两组（GSE31519、GSE76275）三阴性乳腺癌微阵列数据，对信使核糖核酸3'端非翻译区（3'UTR）谱进行评估。将GSE31519数据集327例标本分为164例训练集（演算组）和163例验证集（验算组），将GSE76275数据集164例标本作为测试集（测算组）。通过弹性网络回归模型将6个基因（ADD2、COL1A1、APOL2、IL21R、PKP2、EIF4G3）建立3'UTR组对淋巴结转移风险进行评估。通过接受者操作特征曲线和逻辑回归分析，对基因组和淋巴结转移状态之间的相关性进行评定。
结果发现，6个基因的3'UTR组对于训练集、验证集、测试集的区分能力较强，接受者操作特征曲线下面积分别为0.712、0.729、0.708。按肿瘤大小进行校正后，3'UTR组对于训练集、验证集、测试集的预测能力仍然显著（比值比分别为4.93、4.58、3.59，所有P<0.05）。3'UTR组与肿瘤大小的组合分析，对于训练集、验证集、测试集的准确度分别高达97.2%、100%、100%。
因此，该研究建立了一种基于3'UTR的整合模型，有希望成为可手术三阴性乳腺癌患者淋巴结转移风险的预测工具，低风险患者最有可能避免腋窝手术而获益。虽然仍需进行前瞻研究验证该模型，但是该研究结果可能有助于选择患者避免腋窝手术。
Oncologist. 2018 Aug 6. [Epub ahead of print]
Integrative 3' Untranslated Region-Based Model to Identify Patients with Low Risk of Axillary Lymph Node Metastasis in Operable Triple-Negative Breast Cancer.
Wang L, Hu X, Wang P, Shao ZM.
Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
BACKGROUND: Sentinel lymph node biopsy is the standard surgical staging approach for operable triple-negative breast cancer (TNBC) with clinically negative axillae. In this study, we sought to develop a model to predict TNBC patients with negative nodal involvement, who would benefit from the exemption of the axillary staging surgery.
MATERIALS AND METHODS: We evaluated 3' untranslated region (3'UTR) profiles using microarray data of TNBC from two Gene Expression Omnibus datasets. Samples from GSE31519 were divided into training set (n = 164) and validation set (n = 163), and GSE76275 was used to construct testing set (n = 164). We built a six-member 3'UTR panel (ADD2, COL1A1, APOL2, IL21R, PKP2, and EIF4G3) using an elastic net model to estimate the risk of lymph node metastasis (LNM). Receiver operating characteristic and logistic analyses were used to assess the association between the panel and LNM status.
RESULTS: The six-member 3'UTR-panel showed a high distinguishing power with an area under the curve of 0.712, 0.729, and 0.708 in the training, validation, and testing sets, respectively. After adjustment by tumor size, the 3'UTR panel retained significant predictive power in the training, validation, and testing sets (odds ratio = 4.93, 4.58, and 3.59, respectively; p < .05 for all). A combinatorial analysis of the 3'UTR panel and tumor size yielded an accuracy of 97.2%, 100%, and 100% in training, validation, and testing set, respectively.
CONCLUSION: This study established an integrative 3'UTR-based model as a promising predictor for nodal negativity in operable TNBC. Although a prospective study is needed to validate the model, our results may permit a no axillary surgery option for selected patients.
IMPLICATIONS FOR PRACTICE: Currently, sentinel lymph node biopsy is the standard approach for surgical staging in breast cancer patients with negative axillae. Prediction estimation for lymph node metastasis of breast cancer relies on clinicopathological characteristics, which is unreliable, especially in triple-negative breast cancer (TNBC)-a highly heterogeneous disease. The authors developed and validated an effective prediction model for the lymph node status of patients with TNBC, which integrates 3'UTR markers and tumor size. This is the first 3'UTR-based model that will help identify TNBC patients with low risk of nodal involvement who are most likely to benefit from exemption axillary surgery.
KEYWORDS: 3' untranslated region; Alternative polyadenylation; Lymph node; Prediction modeling; Triple-negative breast cancer
PMID: 30082491
PII: theoncologist.2017-0609
DOI: 10.1634/theoncologist.2017-0609
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