Peng Wenting, Lin Caijin, Jing Shanshan, Su Guanhua, Jin Xi, Di Genhong, Shao Zhiming
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Front Oncol. 2021 Sep 16;11:746763. doi: 10.3389/fonc.2021.746763. eCollection 2021.
BACKGROUND: The prognosis of lymph node-negative triple-negative breast cancer (TNBC) is still worse than that of other subtypes despite adjuvant chemotherapy. Reliable prognostic biomarkers are required to identify lymph node-negative TNBC patients at a high risk of distant metastasis and optimize individual treatment. METHODS: We analyzed the RNA sequencing data of primary tumor tissue and the clinicopathological data of 202 lymph node-negative TNBC patients. The cohort was randomly divided into training and validation sets. Least absolute shrinkage and selection operator Cox regression and multivariate Cox regression were used to construct the prognostic model. RESULTS: A clinical prognostic model, seven-gene signature, and combined model were constructed using the training set and validated using the validation set. The seven-gene signature was established based on the genomic variables associated with distant metastasis after shrinkage correction. The difference in the risk of distant metastasis between the low- and high-risk groups was statistically significant using the seven-gene signature (training set: < 0.001; validation set: = 0.039). The combined model showed significance in the training set ( < 0.001) and trended toward significance in the validation set ( = 0.071). The seven-gene signature showed improved prognostic accuracy relative to the clinical signature in the training data (AUC value of 4-year ROC, 0.879 0.699, = 0.046). Moreover, the composite clinical and gene signature also showed improved prognostic accuracy relative to the clinical signature (AUC value of 4-year ROC: 0.888 0.699, = 0.029; AUC value of 5-year ROC: 0.882 0.693, = 0.038). A nomogram model was constructed with the seven-gene signature, patient age, and tumor size. CONCLUSIONS: The proposed signature may improve the risk stratification of lymph node-negative TNBC patients. High-risk lymph node-negative TNBC patients may benefit from treatment escalation.
背景:尽管进行了辅助化疗,但淋巴结阴性三阴性乳腺癌(TNBC)的预后仍比其他亚型差。需要可靠的预后生物标志物来识别远处转移风险高的淋巴结阴性TNBC患者,并优化个体化治疗。 方法:我们分析了202例淋巴结阴性TNBC患者的原发肿瘤组织RNA测序数据和临床病理数据。该队列被随机分为训练集和验证集。使用最小绝对收缩和选择算子Cox回归及多变量Cox回归构建预后模型。 结果:使用训练集构建了临床预后模型、七基因特征和联合模型,并使用验证集进行验证。七基因特征基于收缩校正后与远处转移相关的基因组变量建立。使用七基因特征时,低风险组和高风险组之间远处转移风险的差异具有统计学意义(训练集:<0.001;验证集:=0.039)。联合模型在训练集中具有显著性(<0.001),在验证集中有显著趋势(=0.071)。在训练数据中,七基因特征相对于临床特征显示出更高的预后准确性(4年ROC的AUC值,0.879对0.699,=0.046)。此外,综合临床和基因特征相对于临床特征也显示出更高的预后准确性(4年ROC的AUC值:0.888对0.699,=0.029;5年ROC的AUC值:0.882对0.693,=0.038)。用七基因特征、患者年龄和肿瘤大小构建了列线图模型。 结论:所提出的特征可能改善淋巴结阴性TNBC患者的风险分层。高风险淋巴结阴性TNBC患者可能从强化治疗中获益。
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