Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer
Abstract HER2-targeted therapies have improved outcomes in metastatic gastric cancer (mGC), yet assessment of HER2 status in tumor tissues remains limited by heterogeneity and temporal changes. This study aimed to evaluate real-time HER2 expression on circulating tumor cells (CTCs) using the On-chip...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-06913-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849335044336779264 |
|---|---|
| author | Yasuaki Kimura Koichi Suzuki Sawako Tamaki Iku Abe Yuhei Endo Kosuke Ichida Yuta Muto Fumiaki Watanabe Masaaki Saito Kazuo Takeda Toshiki Rikiyama |
| author_facet | Yasuaki Kimura Koichi Suzuki Sawako Tamaki Iku Abe Yuhei Endo Kosuke Ichida Yuta Muto Fumiaki Watanabe Masaaki Saito Kazuo Takeda Toshiki Rikiyama |
| author_sort | Yasuaki Kimura |
| collection | DOAJ |
| description | Abstract HER2-targeted therapies have improved outcomes in metastatic gastric cancer (mGC), yet assessment of HER2 status in tumor tissues remains limited by heterogeneity and temporal changes. This study aimed to evaluate real-time HER2 expression on circulating tumor cells (CTCs) using the On-chip Sort system. CTCs were enriched from blood samples of 27 mGC patients, identified by cytokeratin staining, and assessed for HER2 expression via fluorescent labeling. The epithelial-mesenchymal transition (EMT) index was calculated based on co-expression of vimentin and cytokeratin. CTCs also underwent whole-genome amplification and targeted sequencing using a cancer gene panel. Patients were stratified into three groups: Group A (n = 13), HER2-positive in tissue; Group B (n = 8), tissue HER2-negative but CTC HER2-positive; and Group C (n = 6), HER2-negative in both tissue and CTCs. All patients received cytotoxic chemotherapy; only Group A received additional HER2-targeted therapy. Group B showed the poorest progression-free survival (PFS: 7.0 months), compared to Group A (15.7 months) and Group C (not reached). CTC HER2 expression correlated with EMT index; Groups A and B also exhibited higher EMT indices and shared EMT-related mutations. These findings suggest that CTC-based HER2 monitoring reflects tumor aggressiveness and may help identify patients who could benefit from HER2-targeted therapy despite negative tissue HER2 status. |
| format | Article |
| id | doaj-art-e9f1f99520a14a1ba6256498a6945977 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e9f1f99520a14a1ba6256498a69459772025-08-20T03:45:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-06913-xReal-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancerYasuaki Kimura0Koichi Suzuki1Sawako Tamaki2Iku Abe3Yuhei Endo4Kosuke Ichida5Yuta Muto6Fumiaki Watanabe7Masaaki Saito8Kazuo Takeda9Toshiki Rikiyama10Department of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityOn-chip Biotechnologies Co., LtdDepartment of Surgery, Saitama Medical Center, Jichi Medical UniversityAbstract HER2-targeted therapies have improved outcomes in metastatic gastric cancer (mGC), yet assessment of HER2 status in tumor tissues remains limited by heterogeneity and temporal changes. This study aimed to evaluate real-time HER2 expression on circulating tumor cells (CTCs) using the On-chip Sort system. CTCs were enriched from blood samples of 27 mGC patients, identified by cytokeratin staining, and assessed for HER2 expression via fluorescent labeling. The epithelial-mesenchymal transition (EMT) index was calculated based on co-expression of vimentin and cytokeratin. CTCs also underwent whole-genome amplification and targeted sequencing using a cancer gene panel. Patients were stratified into three groups: Group A (n = 13), HER2-positive in tissue; Group B (n = 8), tissue HER2-negative but CTC HER2-positive; and Group C (n = 6), HER2-negative in both tissue and CTCs. All patients received cytotoxic chemotherapy; only Group A received additional HER2-targeted therapy. Group B showed the poorest progression-free survival (PFS: 7.0 months), compared to Group A (15.7 months) and Group C (not reached). CTC HER2 expression correlated with EMT index; Groups A and B also exhibited higher EMT indices and shared EMT-related mutations. These findings suggest that CTC-based HER2 monitoring reflects tumor aggressiveness and may help identify patients who could benefit from HER2-targeted therapy despite negative tissue HER2 status.https://doi.org/10.1038/s41598-025-06913-xAdvanced gastric cancerCirculating tumor cellsHER2Liquid biopsy |
| spellingShingle | Yasuaki Kimura Koichi Suzuki Sawako Tamaki Iku Abe Yuhei Endo Kosuke Ichida Yuta Muto Fumiaki Watanabe Masaaki Saito Kazuo Takeda Toshiki Rikiyama Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer Scientific Reports Advanced gastric cancer Circulating tumor cells HER2 Liquid biopsy |
| title | Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer |
| title_full | Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer |
| title_fullStr | Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer |
| title_full_unstemmed | Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer |
| title_short | Real-time assessment of circulating tumor cells refines the indication for HER2-targeted therapy in metastatic gastric cancer |
| title_sort | real time assessment of circulating tumor cells refines the indication for her2 targeted therapy in metastatic gastric cancer |
| topic | Advanced gastric cancer Circulating tumor cells HER2 Liquid biopsy |
| url | https://doi.org/10.1038/s41598-025-06913-x |
| work_keys_str_mv | AT yasuakikimura realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT koichisuzuki realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT sawakotamaki realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT ikuabe realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT yuheiendo realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT kosukeichida realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT yutamuto realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT fumiakiwatanabe realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT masaakisaito realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT kazuotakeda realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer AT toshikirikiyama realtimeassessmentofcirculatingtumorcellsrefinestheindicationforher2targetedtherapyinmetastaticgastriccancer |