Panoutsopoulou Konstantina, Liu Yueyang, Avgeris Margaritis, Dreyer Tobias, Dorn Julia, Magdolen Viktor, Scorilas Andreas
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Clinical Research Unit, Department of Obstetrics and Gynecology, School of Medicine, Technical University of Munich, Munich, Germany; Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
Clin Biochem. 2023 Apr;114:43-51. doi: 10.1016/j.clinbiochem.2022.12.004. Epub 2022 Dec 8.
In the era of precision medicine, the highly aggressive and heterogenous triple-negative breast cancer (TNBC) is still characterized by limited options to support personalized prognosis and guide therapeutic interventions. Thereafter, the aim of the present study has been the thorough evaluation of miR-146a as a novel molecular indicator of TNBC prognosis and treatment outcome, utilizing four independent TNBC cohorts.
DESIGN & METHODS: miR-146a levels were clinically evaluated in our screening (n = 122) and three external validation TNBC cohorts (de Rinaldis et al. 2013, n = 114; Jézéquel et al. 2015, n = 107; TCGA, n = 180). Analysis of miR-146a and validated gene targets was performed in Jézéquel et al. and TCGA validation cohorts. Patients' survival, recurrence and metastasis were determined as clinical endpoints for the survival analysis. Internal validation was performed by bootstrap analysis and clinical net benefit was evaluated by decision curve analysis.
Reduction of miR-146a is strongly associated with patients' poor survival and can predict post-treatment disease early-recurrence, independently of tumor size, lymph node status, histological grade and patients' age. The analysis of the external validation cohorts corroborated the unfavorable nature of miR-146a repression regarding patients' survival and, strikingly, unveiled the ability of miR-146a to predict TNBC metastasis. Combined assessment of miR-146a levels and lymph node status resulted in superior risk-stratification of TNBC patients and higher clinical benefit regarding disease prognosis and post-treatment outcome. Ultimately, miR-146a was negatively associated with EGFR and SOX2 expression in TNBC.
miR-146a evaluation could ameliorate personalized prognosis and support precision medicine decisions in TNBC.
在精准医学时代，极具侵袭性且异质性的三阴性乳腺癌（TNBC）仍面临支持个性化预后和指导治疗干预的选择有限的问题。因此，本研究的目的是利用四个独立的TNBC队列，全面评估miR-146a作为TNBC预后和治疗结果的新型分子指标。
在我们的筛查队列（n = 122）以及三个外部验证TNBC队列（de Rinaldis等人，2013年，n = 114；Jézéquel等人，2015年，n = 107；TCGA，n = 180）中对miR-146a水平进行临床评估。在Jézéquel等人和TCGA验证队列中对miR-146a及其验证的基因靶点进行分析。将患者的生存、复发和转移确定为生存分析的临床终点。通过自举分析进行内部验证，并通过决策曲线分析评估临床净效益。
miR-146a水平降低与患者的不良生存密切相关，并且可以独立于肿瘤大小、淋巴结状态、组织学分级和患者年龄预测治疗后疾病的早期复发。外部验证队列的分析证实了miR-146a抑制对患者生存的不利性质，并且显著揭示了miR-146a预测TNBC转移的能力。联合评估miR-146a水平和淋巴结状态可实现TNBC患者更好的风险分层，并在疾病预后和治疗后结果方面带来更高的临床效益。最终，miR-146a与TNBC中的EGFR和SOX2表达呈负相关。
miR-146a评估可改善TNBC的个性化预后并支持精准医学决策。
