Yang Lin, Chen Songhao, Wang Meixue, Peng Shujia, Zhao Huadong, Yang Ping, Bao Guoqiang, He Xianli
Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, Shaanxi, China.
Heliyon. 2024 Sep 20;10(19):e38221. doi: 10.1016/j.heliyon.2024.e38221. eCollection 2024 Oct 15.
Despite the approval of several therapeutic agents for HER2-positive breast cancer, drug resistance remains a significant challenge, hindering the patient's prognosis. Thus, our study aimed to establish a risk model to predict the prognosis of patients and identify key genes regulating drug resistance in HER2-positive breast cancer. Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), a predictive model was constructed based on 5 drug resistance-related genes, which demonstrated a notable capacity to indicate the survival rates of patients. Besides, through eccDNA and transcriptome sequencing of drug-sensitive and resistant cancer cells, 3 significant DEGs were identified: MED1, MED24, and NMD3. Among them, MED1 showed the most significant elevation in drug-resistance cells, highlighting its crucial role in mediating drug resistance. MED1 may serve as a valuable target for alleviating drug resistance in HER2-positive breast cancer.
尽管几种治疗药物已获批用于治疗HER2阳性乳腺癌,但耐药性仍然是一个重大挑战,影响着患者的预后。因此,我们的研究旨在建立一个风险模型来预测患者的预后,并确定调节HER2阳性乳腺癌耐药性的关键基因。利用来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的数据,基于5个与耐药性相关的基因构建了一个预测模型,该模型显示出显著的预测患者生存率的能力。此外,通过对药物敏感和耐药癌细胞的eccDNA和转录组测序,鉴定出3个显著差异表达基因:MED1、MED24和NMD3。其中,MED1在耐药细胞中升高最为显著,突出了其在介导耐药性中的关键作用。MED1可能是缓解HER2阳性乳腺癌耐药性的一个有价值的靶点。