Department of General Surgery, the Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Nanjing, China.
Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
J Clin Lab Anal. 2022 Feb;36(2):e24212. doi: 10.1002/jcla.24212. Epub 2022 Jan 7.
Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Trastuzumab-based therapy is a standard treatment for HER2-positive breast cancer, but some patients are resistance to the therapy. There are no known diagnostic biomarkers to improve the early diagnosis of HER2-positive breast cancer and the clinical utility of trastuzumab therapy. Using ultrahigh-performance liquid time of flight mass spectrometry (UPLC-TOF-MS)-based serum metabolomics and multivariate statistical analysis, we investigated and identified the circulating metabolites L-arginine and arachidonic acid were elevated in trastuzumab-responsive and trastuzumab-resistant HER2-positive breast cancer patients, and increased until reaching their peaks in trastuzumab-resistant HER2-positive breast cancer patients. Moreover, an equation for assessing the risk scores based on linear logistic regression models involving L-arginine and arachidonic acid was created, which was beneficial for revealing metabolic changes in HER2-positive breast cancer and enhancing current trastuzumab-based therapy. In summary, we develop serum-based metabolic biomarkers for diagnosis of HER2-positive breast cancers and predicts the therapeutic effects of trastuzumab therapy.
人表皮生长因子受体 2（HER2）阳性是一种特别侵袭性的乳腺癌。曲妥珠单抗为基础的治疗是 HER2 阳性乳腺癌的标准治疗方法，但有些患者对该治疗有耐药性。目前尚无已知的诊断生物标志物来改善 HER2 阳性乳腺癌的早期诊断和曲妥珠单抗治疗的临床应用。本研究采用基于超高效液相飞行时间质谱（UPLC-TOF-MS）的血清代谢组学和多变量统计分析方法，研究并鉴定出曲妥珠单抗反应性和曲妥珠单抗耐药性 HER2 阳性乳腺癌患者血清中升高的循环代谢物 L-精氨酸和花生四烯酸，并在曲妥珠单抗耐药性 HER2 阳性乳腺癌患者中升高至峰值。此外，还创建了一个基于线性逻辑回归模型的评估风险评分的方程，其中涉及 L-精氨酸和花生四烯酸，这有利于揭示 HER2 阳性乳腺癌的代谢变化，并增强目前基于曲妥珠单抗的治疗效果。总之，我们开发了基于血清的代谢生物标志物，用于 HER2 阳性乳腺癌的诊断，并预测曲妥珠单抗治疗的疗效。
