Dynamic changes in serum adenosine and the adenosine metabolism-based signature for prognosis in HER2-positive metastatic breast cancer patients.

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.