HER2阳性乳腺癌患者治疗期间microRNA-497/FGF-23轴的纵向变化及其与新辅助/辅助曲妥珠单抗诱导的心脏毒性的关联
Longitude Variation of the microRNA-497/FGF-23 Axis during Treatment and Its Linkage with Neoadjuvant/Adjuvant Trastuzumab-Induced Cardiotoxicity in HER2-Positive Breast Cancer Patients.
作者信息
Liu Hui, Hu Xiaoyan, Wang Lingyun, Du Tao, Feng Jing, Li Ming, Liu Lei, Liu Xiaofang
机构信息
Hematology and Oncology Department, The First People's Hospital of Guiyang, Guiyang, China.
出版信息
Front Surg. 2022 May 11;9:862617. doi: 10.3389/fsurg.2022.862617. eCollection 2022.
PURPOSE
MicroRNA-497 (miR-497) is previously reported to target fibroblast growth factor 23 (FGF-23) and regulates cardiac injury, while their value in predicting drug-induced cardiotoxicity is not reported. Thus, the current study aimed to investigate the correlation of miR-497/FGF-23 with neoadjuvant/adjuvant trastuzumab-induced cardiotoxicity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients.
METHODS
A total of 97 HER2-positive surgical breast cancer patients who received neoadjuvant/adjuvant trastuzumab contained regimens were enrolled; then, their peripheral blood mononuclear cells (PBMC) and serum were collected at baseline, after neoadjuvant treatment, at 3 months (M3), 6 months (M6), 9 months (M9), and 12 months (M12) after surgery. The PBMC was used for miR-497 measurements, and the serum was used for FGF-23 measurements. The cardiotoxicity events and incidence were recorded.
RESULTS
A total of 24 (24.7%) patients occurred cardiotoxicity during the treatment period. MiR-497 decreased from baseline (median: 0.955) to M12 after surgery (median: 0.602) (< 0.001), while FGF-23 increased from baseline (median: 0.390 ng/mL) to M12 after surgery (median: 0.566 ng/mL) (< 0.001); besides, the miR-497/FGF-23 axis greatly reduced from baseline (median: 2.545) to M12 after surgery (median: 1.222) (< 0.001). At most time points, miR-497 was negatively related to FGF-23 (all < 0.05). Notably, the miR-497/FGF-23 axis at all time points (including baseline, postneoadjuvant treatment, M3, M6, M9, and M12) was related to a lower risk of cardiotoxicity (all < 0.05). Furthermore, the miR-497/FGF-23 axis was also positively correlated with the left ventricular ejection fraction (LVEF) at all time points (all < 0.01).
CONCLUSION
The MiR-497/FGF-23 axis serves as a potential indicator predicting trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.
目的
先前有报道称，微小RNA-497（miR-497）靶向成纤维细胞生长因子23（FGF-23）并调节心脏损伤，但其在预测药物性心脏毒性方面的价值尚未见报道。因此，本研究旨在探讨miR-497/FGF-23与新辅助/辅助曲妥珠单抗诱导的人表皮生长因子受体2（HER2）阳性乳腺癌患者心脏毒性的相关性。
方法
共纳入97例接受新辅助/辅助曲妥珠单抗联合治疗方案的HER2阳性乳腺癌手术患者；然后，在基线、新辅助治疗后、术后3个月（M3）、6个月（M6）、9个月（M9）和12个月（M12）采集其外周血单个核细胞（PBMC）和血清。PBMC用于检测miR-497，血清用于检测FGF-23。记录心脏毒性事件及发生率。
结果
共有24例（24.7%）患者在治疗期间发生心脏毒性。miR-497从基线（中位数：0.955）降至术后M12（中位数：0.602）（<0.001），而FGF-23从基线（中位数：0.390 ng/mL）升至术后M12（中位数：0.566 ng/mL）（<0.001）；此外，miR-497/FGF-23轴从基线（中位数：2.545）大幅降至术后M12（中位数：1.222）（<0.001）。在大多数时间点，miR-497与FGF-23呈负相关（均<0.05）。值得注意的是，所有时间点（包括基线、新辅助治疗后、M3、M6、M9和M12）的miR-497/FGF-23轴与较低的心脏毒性风险相关（均<0.05）。此外，miR-497/FGF-23轴在所有时间点也与左心室射血分数（LVEF）呈正相关（均<0.01）。
结论
MiR-497/FGF-23轴可作为预测HER2阳性乳腺癌患者曲妥珠单抗诱导的心脏毒性的潜在指标。
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