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Abstract：
This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.
摘要：
本研究论文提出了一种新的方法来识别可用于预测有资格接受新辅助治疗的三阴性乳腺癌（TNBC）患者的生物标志物。该研究利用了一组TNBC患者的生存和RNA测序数据，并鉴定了276个基因，这些基因的表达与这些患者的生存有关。然后基于无翼/整合途径(Wnt途径)和间充质(Mes)标志物(Wnt/Mes)的存在或不存在,使用基因表达数据将患者分为两个主要组。Wnt/Mes相关基因低表达的患者具有良好的预后，在随访期间没有观察到死亡，而Wnt/Mes基因高表达的患者在19个月内的死亡率更高，为50％。鉴定的基因列表可以被验证，并可能用于确定符合新辅助治疗条件的TNBC患者的治疗选择，从而为开发更有效的TNBC治疗提供有价值的见解。我们的数据还显示化疗前后基因表达谱的显著变化，大多数肿瘤转变为更多的间充质/干细胞样特征。为了验证这一观察，我们使用基因表达数据,在治疗前和治疗后的微阵列50预测分析(PAM50)分子类别中进行了芯片分析以对乳腺癌肿瘤进行分类.我们的发现表明，在药物干预和转移后，某些肿瘤经历了向替代亚型的转变，导致疗效下降。这强调了重新评估化疗后复发或转移的患者的必要性。专注于分子亚型。基于这些完善的亚型定制治疗策略对于优化受影响个体的治疗结果至关重要。
