An Initial Evaluation of Human Plasma cMLC-1: A Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression.
An Initial Evaluation of Human Plasma cMLC-1: A Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression.
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DOI：
10.3389/fonc.2022.809715
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发表时间：
2022
影响因子：
4.7
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中科院分区：
文献类型：
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曲妥珠单抗是人表皮生长因子受体2（HER 2）阳性乳腺癌的靶向治疗。然而，当曲妥珠单抗作为单药或与蒽环类药物联合给药时，已报告曲妥珠单抗诱导的心脏毒性（TIC）。目前没有用于检测TIC的早期发作的手段，例如蛋白质生物标志物。在这方面，基于初步动物研究的有希望的结果，评价了心肌肌球蛋白轻链1（cMLC-1）作为生物标志物预测TIC、筛查乳腺癌患者和监测乳腺癌患者肿瘤进展的潜力。使用酶联免疫吸附试验（ELISA）分析了15例有或无心脏毒性的HER 2+患者在曲妥珠单抗治疗前后不同固定时间点采集的存档血浆样本、79例乳腺癌患者（40例HER 2+，39例HER 2-）最近采集的血浆样本和46例健康供体的cMLC-1水平。在7例曲妥珠单抗治疗的HER 2+乳腺癌患者中，发现3例（43%）血浆cMLC-1水平升高与TIC相关。然而，这项研究为我们研究乳腺癌患者的血浆cMCL-1水平提供了机会。已证实血浆cMCL-1升高与乳腺癌相关。cMLC-1的临界浓度估计为44.99 ng/mL，敏感性为59.49%（95%CI：48.47%-69.63%），特异性为71.74%（95%CI：57.45%-82.68%）。我们还发现，在给定的样本量下，HER 2-乳腺癌患者的血浆cMCL-1水平明显高于HER 2+乳腺癌患者，但不显著。因此，cMLC-1预测HER 2-乳腺癌的灵敏度提高了79.49%（95%CI：64.47%-89.22%），特异性提高了63.04%（95%CI：48.60%-75.48%），临界值为37.17 ng/mL。此外，该研究确定，转移性乳腺癌患者中的cMLC-1水平显著高于非转移性乳腺癌患者。虽然对有限数量的曲妥珠单抗治疗的HER 2+乳腺癌患者血浆中的cMLC-1水平的分析未能完全支持其作为预测TIC的血液蛋白生物标志物的鉴定，但对血浆cMLC-1水平的额外分析确实显著确立了其与乳腺癌和疾病进展的相关性。我们的发现在一定程度上揭示并填补了cMLC-1作为筛查乳腺癌和监测乳腺癌疾病进展的血液蛋白生物标志物的潜力的知识空白差距。
Trastuzumab is a targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab-induced cardiotoxicity (TIC) has been reported when trastuzumab is administered to patients as a single agent or combined with anthracycline. Currently no means for detecting the early onset of TIC such as a protein biomarker is available. In this regard and based on promising results from a preliminary animal study, the potential of cardiac myosin light chain 1(cMLC-1) as a biomarker to predict TIC, screen patients for breast cancer and monitor tumor progression in breast cancer patients was evaluated. Archived plasma samples collected before and after trastuzumab treatment at various fixed time points from 15 HER2+ patients with or without cardiotoxicity, recently collected plasma samples from 79 breast cancer patients (40 HER2+, 39 HER2-), and 46 healthy donors were analyzed for cMLC-1 levels using an enzyme-linked immunosorbent assay (ELISA). An elevated plasma cMLC-1 level was found to be associated with TIC in 3 out of 7 (43%) trastuzumab-treated HER2+ breast cancer patients. However, this study provided an opportunity for us to study plasma cMCL-1 levels in breast cancer patients. It was demonstrated that elevated plasma cMCL-1 is associated with breast cancer. The cutoff cMLC-1 concentration is estimated to be 44.99 ng/mL with a sensitivity of 59.49% (95%CI: 48.47%-69.63%) and specificity of 71.74% (95%CI: 57.45% -82.68%). We also found a noticeable but not significantly more elevated plasma cMCL-1 level in HER2- than in HER2+ breast cancer patients with the given sample sizes. As a result, improved sensitivity of 79.49% (95%CI: 64.47%-89.22%) with the specificity of 63.04% (95%CI:48.60%-75.48%) were obtained for cMLC-1 to predict HER2- breast cancer with the cutoff at 37.17 ng/mL. Moreover, this study determined that cMLC-1 level was significantly higher in patients with metastatic breast cancer than in patients with non-metastatic breast cancer. While the analysis of cMLC-1 levels in the plasma of a limited number of trastuzumab-treated HER2+ breast cancer patients failed to fully support its identification as a blood protein biomarker for predicting TIC, additional analyses of plasma cMLC-1 levels did significantly establish its correlations with breast cancer and disease progression. Our findings shed light on and filled, to some extent, the gap of knowledge of the potential of cMLC-1 as a blood protein biomarker for screening breast cancer and monitoring disease progression of breast cancer.
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影响因子：
45.3
作者：
Seidman, A;Hudis, C;Keefe, D
通讯作者：
Keefe, D
影响因子：
3.7
作者：
DeCara, Jeanne M.
通讯作者：
DeCara, Jeanne M.
影响因子：
4.6
作者：
Wolff, Antonio C.;Hammond, M. Elizabeth Hale;Dowsett, Mitchell
通讯作者：
Dowsett, Mitchell
影响因子：
2.8
作者：
KATUS, HA;YASUDA, T;KHAW, BA
通讯作者：
KHAW, BA
DOI：
10.1093/jnci/djs317
发表时间：
2012-09-05
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Bowles EJ;Wellman R;Feigelson HS;Onitilo AA;Freedman AN;Delate T;Allen LA;Nekhlyudov L;Goddard KA;Davis RL;Habel LA;Yood MU;McCarty C;Magid DJ;Wagner EH;Pharmacovigilance Study Team
通讯作者：
Pharmacovigilance Study Team