Wang Lijun, Ge Yizhi, Yin Li, Zong Dan, Li Yang, Wu Jianfeng, He Xia
Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, China.
Heliyon. 2024 Oct 24;10(23):e39545. doi: 10.1016/j.heliyon.2024.e39545. eCollection 2024 Dec 15.
Adenosine metabolism in the breast cancer microenvironment is critical for tumor immunity. However, the prognostic significance of adenosine in breast cancer remains unclear. We aimed to dynamically monitor serum adenosine levels in patients with HER2-positive metastatic breast cancer (MBC) patients and to explore its predictive significance in trastuzumab therapy.
The sequencing and clinical data were downloaded from TCGA and GSE176078. Adenosine-related differentially expressed genes was analyzed by "DESeq2" package. Multivariate Cox and lasso-penalized Cox regressions were used to construct prognostic risk signatures. The risk scores were calculated from the identified expression of the hub genes. Bioinformatic analyses were performed using R with related packages. We also enrolled the metastatic breast cancer patients with HER2-positive from in our center and classified them into different groups according to the clinical outcomes assessed by enhanced CT. The adenosine levels were dynamically detected, and the difference in immune microenvironment between the subgroups was assessed by the immune cells that were recorded in our center.
A total of 109 breast cancer patients with HER2-positive MBC were enrolled, and the expressions of 22 adenosine-related genes were filtered and matched from the TCGA database. The survival model based on the 15 differentially expressed genes was established, and the risk scores of each patient were the prognostic risk factors. Single-cell transcriptome sequencing data identified transcriptomic differences in patients with HER2-positive breast cancer. We also confirmed the predictive value of serum adenosine in the clinical progression of HER2-positive MBC patients. The different immune microenvironment between the subgroups supported the reliability of the predictive ability of adenosine in HER2-positive MBC patients.
The dynamic change of adenosine is a predictive biomarker for monitoring disease progression. The adenosine metabolism-based signature has the potential application in the prognosis of HER2-positive MBC patients.
乳腺癌微环境中的腺苷代谢对肿瘤免疫至关重要。然而，腺苷在乳腺癌中的预后意义仍不明确。我们旨在动态监测HER2阳性转移性乳腺癌（MBC）患者的血清腺苷水平，并探讨其在曲妥珠单抗治疗中的预测意义。
从TCGA和GSE176078下载测序和临床数据。使用“DESeq2”软件包分析腺苷相关差异表达基因。采用多变量Cox回归和套索惩罚Cox回归构建预后风险特征。根据鉴定出的核心基因表达计算风险评分。使用R及相关软件包进行生物信息学分析。我们还纳入了本中心HER2阳性的转移性乳腺癌患者，并根据增强CT评估的临床结果将他们分为不同组。动态检测腺苷水平，并通过本中心记录的免疫细胞评估亚组间免疫微环境的差异。
共纳入109例HER2阳性MBC乳腺癌患者，从TCGA数据库中筛选并匹配了22个腺苷相关基因的表达。基于15个差异表达基因建立了生存模型，每位患者的风险评分是预后危险因素。单细胞转录组测序数据确定了HER2阳性乳腺癌患者的转录组差异。我们还证实了血清腺苷在HER2阳性MBC患者临床进展中的预测价值。亚组间不同的免疫微环境支持了腺苷对HER2阳性MBC患者预测能力的可靠性。
腺苷的动态变化是监测疾病进展的预测生物标志物。基于腺苷代谢的特征在HER2阳性MBC患者的预后中具有潜在应用价值。
