Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer
Abstract Background Circulating tumor cells (CTCs) has been demonstrated as a promising liquid biopsy marker for breast cancer (BC). However, the intra-patient heterogeneity of CTCs remains a challenge to clinical application. We aim at profiling aggressive CTCs subpopulation in BC utilizing the dis...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-020-02237-8 |
| _version_ | 1819275578761543680 |
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| author | Jing Chen Changsheng Ye Jianyu Dong Shunwang Cao Yanwei Hu Bo Situ Xiaoxue Xi Sihua Qin Jiasen Xu Zhen Cai Lei Zheng Qian Wang |
| author_facet | Jing Chen Changsheng Ye Jianyu Dong Shunwang Cao Yanwei Hu Bo Situ Xiaoxue Xi Sihua Qin Jiasen Xu Zhen Cai Lei Zheng Qian Wang |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | Abstract Background Circulating tumor cells (CTCs) has been demonstrated as a promising liquid biopsy marker for breast cancer (BC). However, the intra-patient heterogeneity of CTCs remains a challenge to clinical application. We aim at profiling aggressive CTCs subpopulation in BC utilizing the distinctive metabolic reprogramming which is a hallmark of metastatic tumor cells. Methods Oncomine, TCGA and Kaplan–Meier plotter databases were utilized to analyze expression and survival relevance of the previously screened metastasis-promoting metabolic markers (PGK1/G6PD) in BC patients. CTCs detection and metabolic classification were performed through micro-filtration and multiple RNA in situ hybridization using CD45 and PGK1/G6PD probes. Blood samples were collected from 64 BC patients before treatment for CTCs analysis. Patient characteristics were recorded to evaluate clinical applications of CTCs metabolic subtypes, as well as morphological EMT subtypes classified by epithelial (EpCAM/CKs) and mesenchymal (Vimentin/Twist) markers. Results PGK1 and G6PD expressions were up-regulated in invasive BC tissues compared with normal mammary tissues. Increased tissue expressions of PGK1 or G6PD indicated shortened overall and relapse-free survival of BC patients (P < 0.001). Blood GM+CTCs (DAPI+CD45−PGK1/G6PD+) was detectable (range 0–54 cells/5 mL) in 61.8% of tCTCs > 0 patients. Increased GM+CTCs number and positive rate were correlated with tumor metastasis and progression (P < 0.05). The GM+CTCs ≥ 2/5 mL level presented superior AUC of ROC at 0.854 (95% CI 0.741–0.968) in the diagnosis of BC metastasis (sensitivity/specificity: 66.7%/91.3%), compared with that of tCTCs (0.779) and CTCs-EMT subtypes (E-CTCs 0.645, H-CTCs 0.727 and M-CTCs 0.697). Moreover, GM+CTCs+ group had inferior survival with decreased 2 years-PFS proportion (18.5%) than GM+CTCs− group (87.9%; P = 0.001). Conclusions This work establishes a PGK1/G6PD-based method for CTCs metabolic classification to identify the aggressive CTCs subpopulation. Metabolically active GM+CTCs subtype is suggested a favorable biomarker of distant metastasis and prognosis in BC patients. |
| first_indexed | 2024-12-23T23:26:33Z |
| format | Article |
| id | doaj.art-41742ecf10d9460490ff67c4c315b04e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-23T23:26:33Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-41742ecf10d9460490ff67c4c315b04e2022-12-21T17:26:13ZengBMCJournal of Translational Medicine1479-58762020-02-0118111410.1186/s12967-020-02237-8Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancerJing Chen0Changsheng Ye1Jianyu Dong2Shunwang Cao3Yanwei Hu4Bo Situ5Xiaoxue Xi6Sihua Qin7Jiasen Xu8Zhen Cai9Lei Zheng10Qian Wang11Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Breast Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Breast Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese MedicineLaboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityLaboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityLaboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityDepartment of Laboratory Medicine, Zhujiang Hospital, Southern Medical UniversitySurExam Bio-Tech, Guangzhou Technology Innovation Base, Science CityLaboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityLaboratory Medicine Center, Nanfang Hospital, Southern Medical UniversityDepartment of Laboratory Medicine, Zhujiang Hospital, Southern Medical UniversityAbstract Background Circulating tumor cells (CTCs) has been demonstrated as a promising liquid biopsy marker for breast cancer (BC). However, the intra-patient heterogeneity of CTCs remains a challenge to clinical application. We aim at profiling aggressive CTCs subpopulation in BC utilizing the distinctive metabolic reprogramming which is a hallmark of metastatic tumor cells. Methods Oncomine, TCGA and Kaplan–Meier plotter databases were utilized to analyze expression and survival relevance of the previously screened metastasis-promoting metabolic markers (PGK1/G6PD) in BC patients. CTCs detection and metabolic classification were performed through micro-filtration and multiple RNA in situ hybridization using CD45 and PGK1/G6PD probes. Blood samples were collected from 64 BC patients before treatment for CTCs analysis. Patient characteristics were recorded to evaluate clinical applications of CTCs metabolic subtypes, as well as morphological EMT subtypes classified by epithelial (EpCAM/CKs) and mesenchymal (Vimentin/Twist) markers. Results PGK1 and G6PD expressions were up-regulated in invasive BC tissues compared with normal mammary tissues. Increased tissue expressions of PGK1 or G6PD indicated shortened overall and relapse-free survival of BC patients (P < 0.001). Blood GM+CTCs (DAPI+CD45−PGK1/G6PD+) was detectable (range 0–54 cells/5 mL) in 61.8% of tCTCs > 0 patients. Increased GM+CTCs number and positive rate were correlated with tumor metastasis and progression (P < 0.05). The GM+CTCs ≥ 2/5 mL level presented superior AUC of ROC at 0.854 (95% CI 0.741–0.968) in the diagnosis of BC metastasis (sensitivity/specificity: 66.7%/91.3%), compared with that of tCTCs (0.779) and CTCs-EMT subtypes (E-CTCs 0.645, H-CTCs 0.727 and M-CTCs 0.697). Moreover, GM+CTCs+ group had inferior survival with decreased 2 years-PFS proportion (18.5%) than GM+CTCs− group (87.9%; P = 0.001). Conclusions This work establishes a PGK1/G6PD-based method for CTCs metabolic classification to identify the aggressive CTCs subpopulation. Metabolically active GM+CTCs subtype is suggested a favorable biomarker of distant metastasis and prognosis in BC patients.https://doi.org/10.1186/s12967-020-02237-8Circulating tumor cells typingMetabolic reprogrammingBreast cancer |
| spellingShingle | Jing Chen Changsheng Ye Jianyu Dong Shunwang Cao Yanwei Hu Bo Situ Xiaoxue Xi Sihua Qin Jiasen Xu Zhen Cai Lei Zheng Qian Wang Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer Journal of Translational Medicine Circulating tumor cells typing Metabolic reprogramming Breast cancer |
| title | Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| title_full | Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| title_fullStr | Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| title_full_unstemmed | Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| title_short | Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| title_sort | metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer |
| topic | Circulating tumor cells typing Metabolic reprogramming Breast cancer |
| url | https://doi.org/10.1186/s12967-020-02237-8 |
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