An Initial Evaluation of Human Plasma cMLC-1: A Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression.

Autor:	Yu L; Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.; Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy, Southwest University, Chongqing, China., Allen R; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Jia L; Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Sun T; Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Isakoff SJ; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Scherrer-Crosbie M; Perelman Center for Advanced Medicine, Cardiovascular Medicine Division, The Hospital of the University of Pennsylvania, Philadelphia, PA, United States., Kehlmann AM; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Zheng H; Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Ly A; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Walmsley CS; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Hesler K; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Varasteh AN; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Pinto CJ; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., McLoughlin DE; Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, United States., Wu W; Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, United States., Wang X; Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 May 03; Vol. 12, pp. 809715. Date of Electronic Publication: 2022 May 03 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.809715
Abstrakt:	Background: 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. Methods: 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). Results: 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. Conclusions: 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yu, Allen, Jia, Sun, Isakoff, Scherrer-Crosbie, Kehlmann, Zheng, Ly, Walmsley, Hesler, Varasteh, Pinto, McLoughlin, Wu and Wang.)
Databáze:	MEDLINE
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