Li Liyan, Lyu Hongwei, Chen Qian, Bai Yating, Yu Jing, Cai Ruigang
Beijing Pinggu District Maternal and Child Health Care Hospital, Beijing, China.
Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
J Breast Cancer. 2025 Apr;28(2):61-71. doi: 10.4048/jbc.2024.0177. Epub 2025 Mar 4.
This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer.
We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses.
The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups ( = 0.008 and = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of and were significantly lower in the long-term survival group than those in the short-term survival group ( = 0.029 and = 0.024, respectively). CREB-regulated transcription coactivator 1 () mutations occurred significantly more frequently in the chemotherapy-resistant group ( = 0.027) and were associated with shorter progression-free survival ( = 0.036). Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group ( = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced ( = 0.002 and < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway.
This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in and could serve as biomarkers for breast cancer prognosis, while mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.
本研究旨在调查与乳腺癌更好预后相关的分子特征。
我们对56个样本中的962个基因进行了靶向测序，将它们分为长期生存组和短期生存组以及化疗敏感组和化疗耐药组以进行进一步分析。
结果表明，短期生存组和化疗耐药组的肿瘤突变负荷值显著更高（分别为P = 0.008和P = 0.003）。体细胞突变分析显示，长期生存组中TP53和PIK3CA的突变频率显著低于短期生存组（分别为P = 0.029和P = 0.024）。CREB调节的转录共激活因子1（CRTC1）突变在化疗耐药组中发生的频率显著更高（P = 0.027），并且与无进展生存期较短相关（P = 0.036）。特征加权分析显示Signature.3显著增加，其与化疗敏感组中的同源重组修复缺陷相关（P = 0.045）。相反，与有效的DNA修复机制相关的特征Signature.1和Signature.15显著降低（分别为P = 0.002和P < 0.001）。京都基因与基因组百科全书通路分析表明，基因突变在JAK-STAT信号通路中显著富集。
本研究通过组间比较分析发现，免疫疗法（使用程序性死亡1/程序性死亡配体1抑制剂）可能改善短期生存和化疗耐药患者的预后。此外，研究表明TP53和PIK3CA的突变可作为乳腺癌预后的生物标志物，而CRTC1突变和Signature.3可预测化疗反应。该研究还发现JAK-STAT通路可能是化疗耐药的潜在治疗靶点。因此，本研究确定了影响乳腺癌患者预后的分子特征，为制定个性化治疗策略提供了重要的理论见解。
