Liu Yueyang, Gong Weiwei, Panoutsopoulou Konstantina, Singer-Cornelius Thirza, Augustin Katharina, Bronger Holger, Kiechle Marion, Dorn Julia, Scorilas Andreas, Avgeris Margaritis, Magdolen Viktor, Dreyer Tobias
Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich Munich, Germany.
Department of Gynecology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences Guangzhou, Guangdong, People's Republic of China.
Am J Cancer Res. 2023 Jun 15;13(6):2471-2487. eCollection 2023.
Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, associated with early metastasis and recurrence as well as poor patient outcome. TNBC does not or weakly respond to hormonal or HER2-targeted therapies. Therefore, there is a strong need to identify other potential molecular targets for TNBC therapy. Micro-RNAs play important roles in the post-transcriptional regulation of gene expression. Thus, micro-RNAs, displaying an association between elevated expression and poor patient prognosis, may represent candidates for such novel tumor targets. In the present study, we evaluated the prognostic impact of miR-27a, miR-206, and miR-214 in TNBC via qPCR in tumor tissue (n=146). In univariate Cox regression analysis, elevated expression of all three analyzed micro-RNAs was significantly associated with shortened disease-free survival (hazard ratio [HR] for miR-27a: 1.85, P=0.038; miR-206: 1.83, P=0.041; miR-214: 2.06, P=0.012). In multivariable analysis, the micro-RNAs remained independent biomarkers for disease-free survival (HR for miR-27a: 1.99, P=0.033; miR-206: 2.14, P=0.018; miR-214: 2.01, P=0.026). Furthermore, our results suggest that elevated levels of these micro-RNAs are linked to enhanced resistance to chemotherapy. Based on the association of high expression levels with shortened patient survival and increased chemoresistance, miR-27a, miR-206, and miR-214 may represent novel molecular targets for TNBC.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，与早期转移、复发以及患者预后不良相关。TNBC对激素治疗或HER2靶向治疗无反应或反应微弱。因此，迫切需要确定TNBC治疗的其他潜在分子靶点。微小RNA在基因表达的转录后调控中发挥重要作用。因此，微小RNA表达升高与患者预后不良相关，可能是这类新型肿瘤靶点的候选者。在本研究中，我们通过qPCR评估了miR-27a、miR-206和miR-214在肿瘤组织（n=146）中对TNBC的预后影响。在单变量Cox回归分析中，所有三种分析的微小RNA表达升高均与无病生存期缩短显著相关（miR-27a的风险比[HR]：1.85，P=0.038；miR-206：1.83，P=0.041；miR-214：2.06，P=0.012）。在多变量分析中，这些微小RNA仍然是无病生存期的独立生物标志物（miR-27a的HR：1.99，P=0.033；miR-206：2.14，P=0.018；miR-214：2.01，P=0.026）。此外，我们的结果表明，这些微小RNA水平升高与化疗耐药性增强有关。基于高表达水平与患者生存期缩短和化疗耐药性增加的关联，miR-27a、miR-206和miR-214可能是TNBC的新型分子靶点。
