Sun Lu, Chen Xinxu, Li Fei, Liu Shengchun
Department of Breast Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong, China.
Department of the Breast and Thyroid Surgery, Guiqian International General Hospital, 550018, Guiyang, China.
J Formos Med Assoc. 2025 Apr;124(4):361-374. doi: 10.1016/j.jfma.2024.05.007. Epub 2024 May 21.
BACKGROUND/PURPOSE: Cuproptosis may play a significant role in breast cancer (BC). We aimed to investigate the prognostic impact of cuproptosis-related lncRNAs in BC.
Consensus clustering analysis categorized TCGA-BRCA samples into 3 clusters, followed by survival and immune analyses of the 3 clusters. LASSO-COX analysis was performed on cuproptosis-related lncRNAs differentially expressed in BC to construct a BC prognostic model. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment, immune, and drug prediction analyses were performed on the high-risk and low-risk groups. Cell experiments were conducted to analyze the results of drug prediction and two cuproptosis-related lncRNAs (AC104211.1 and LINC01863).
Significant differences were observed in survival outcomes and immune infiltration levels among the three clusters (p < 0.05). The validation of the model showed significant differences in survival outcomes between the high-risk and low-risk groups in both the training and validation sets (p < 0.05). Differential mRNAs between the two groups were significantly enriched in the Neuroactive ligand-receptor interaction and cAMP signaling pathway. Additionally, significant differences were found in immune infiltration levels, human leukocyte antigen (HLA) expression, Immunophenoscore (IPS) scores, and Tumor Immune Dysfunction and Exclusion (TIDE) scores between the two groups (p < 0.05). Drug prediction and corresponding cell experimental results showed that Trametinib, 5-fluorouracil, and AICAR significantly inhibited the viability of MCF-7 cells (p < 0.05). AC104211.1 and LINC01863 were found to impact the proliferation of BC cells.
The risk-scoring model obtained in this study may serve as a robust prognostic biomarker, potentially aiding in clinical decision-making for BC patients.
背景/目的：铜死亡可能在乳腺癌（BC）中发挥重要作用。我们旨在研究与铜死亡相关的长链非编码RNA（lncRNA）对BC预后的影响。
共识聚类分析将TCGA-BRCA样本分为3个簇，随后对这3个簇进行生存和免疫分析。对BC中差异表达的与铜死亡相关的lncRNA进行LASSO-COX分析，以构建BC预后模型。对高危和低危组进行基因本体论/京都基因与基因组百科全书（GO/KEGG）富集、免疫和药物预测分析。进行细胞实验以分析药物预测结果以及两个与铜死亡相关的lncRNA（AC104211.1和LINC01863）。
三个簇之间在生存结局和免疫浸润水平上观察到显著差异（p<0.05）。模型验证显示，在训练集和验证集中，高危组和低危组之间的生存结局存在显著差异（p<0.05）。两组之间的差异mRNA在神经活性配体-受体相互作用和cAMP信号通路中显著富集。此外，两组之间在免疫浸润水平、人类白细胞抗原（HLA）表达、免疫表型评分（IPS）和肿瘤免疫功能障碍与排除（TIDE）评分方面也存在显著差异（p<0.05）。药物预测和相应的细胞实验结果表明，曲美替尼、5-氟尿嘧啶和AICAR显著抑制MCF-7细胞的活力（p<0.05）。发现AC104211.1和LINC01863影响BC细胞的增殖。
本研究中获得的风险评分模型可能作为一个可靠的预后生物标志物，潜在地有助于BC患者的临床决策。
