ORIGINAL RESEARCH article
Front. Med.
Sec. Precision Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1672955
Detecting HER2-positive Circulating Tumor Cells in Gastric Cancer Using a Flow Cytometry-Based Approach
Provisionally accepted
Jan-Mou Lee1
Chia-Chun Tu1Chih-Hao Fang1Shian-Ren Lin1Shiu-Lan Wang1Wan-Yu Lai1Po-Wei Tseng1Wan-En Liao1Li-Yun Huang1Yee Chao1,2,3
Ming-Huang Chen3,4*- 1FullHope Biomedical Co., Ltd., New Taipei City, Taiwan
- 2Central Clinic and Hospital, Taipei City, Taiwan
- 3Taipei Veterans General Hospital, Taipei City, Taiwan
- 4National Yang Ming Chiao Tung University, Hsinchu, Taiwan
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Background HER2 overexpression predicts the response to trastuzumab in gastric cancer (GC); however, assessing this overexpression requires invasive immunohistochemistry. Circulating tumor cells (CTCs) share comparable proteomic phenotypes to those of the primary tumor and represent a less invasive method for evaluating HER2 expression. Nevertheless, methods for detecting HER2 expression on CTCs still require further investigation. Methods A flow cytometry method for detecting HER2-overexpressed CTCs was established by spiking NCI-N87 cells into blood from cancer-naive donors. The method was then applied to blood samples from 14 gastric cancer (GC) patients (4 with HER2-overexpressed tumors and 10 with HER2-wild type tumors) and 10 cancer-naive participants (CNPs), with all data analyzed using one-way ANOVA. Results The gating strategy was defined as CD45−CK-7/8+CK-14/15/16/19+EpCAM+HER2+, with a cutoff value of 5 cells/mL. Using this in-house method, we detected HER2-overexpressed CTCs in 4 of 4 GC patients with HER2-overexpressed tumors (ranging from 8 to 29 cells/mL), while 10 of 10 CNPs had undetectable HER2-overexpressed CTCs. Among GC participants with HER2-wild type tumors, 7 of 10 GC participants had undetectable HER2-overexpressed CTCs, whereas 3 of 10 had detectable HER2-overexpressed CTCs. Furthermore, one participant with HER2-overexpressed CTCs detected by our in-house method received HER2-based targeted therapy and experienced an objective response and was free from disease progression to the date of article writing. Conclusion This study introduces a noninvasive method for monitoring HER2 expression in GC, offering new insights into providing personalized treatment strategies.
Keywords: circulating tumor cells, Flow Cytometry, gastric cancer, HER2 overexpression, liquid biopsy
Received: 25 Jul 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Lee, Tu, Fang, Lin, Wang, Lai, Tseng, Liao, Huang, Chao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ming-Huang Chen, Taipei Veterans General Hospital, Taipei City, Taiwan
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