Effect of 1H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients

• Published in: Cancer science Vol. 114; no. 10; pp. 3924 - 3934
• Main Authors: Tian, Zhenluan, Rao, Qunxian, He, Zhanghai, Zhao, Wei, Chen, Liangyu, Liu, Jieqiong, Wang, Ying
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 28-08-2023; John Wiley and Sons Inc
• Subjects: Apoptosis; Asparagine; Biomarkers; Breast cancer; Cancer therapies; Chemotherapy; Confidence intervals; Cytotoxicity; Immunoglobulins; Immunotherapy; Ligands; Lipoproteins; Lymphocytes; Magnetic resonance spectroscopy; Medical prognosis; Metabolism; Metabolites; Metastasis; Mutation; NMR; Nuclear magnetic resonance; Oncology; Original; PD-1 protein; Proteins; Proteomics; Response rates; Sarcosine; Spectrum analysis; Survival; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; China
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15937

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.