Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics
| العنوان: | Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics |
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| المؤلفون: | Yu Dong, Ziming Li, Chunying Wang, Qihui Shi, Yin Tang, Jie Chen, Shun Lu, Baojun Wu, Xiang Lu, Zhuo Wang, Min Xue, Liu Yang, Zhili Guo, Wei Wei |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Lung Neoplasms, medicine.medical_treatment, General Physics and Astronomy, Cell Count, Kaplan-Meier Estimate, 02 engineering and technology, B7-H1 Antigen, Targeted therapy, Transcriptome, lcsh:Science, Aged, 80 and over, Multidisciplinary, Biological techniques, Middle Aged, Prognosis, 021001 nanoscience & nanotechnology, Cancer metabolism, Cell killing, Adenocarcinoma, Female, Single-Cell Analysis, 0210 nano-technology, Adult, Tumour heterogeneity, Science, Adenocarcinoma of Lung, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Medical research, Proto-Oncogene Proteins, Biomarkers, Tumor, medicine, Humans, Metabolomics, Liquid biopsy, Lung cancer, Aged, business.industry, Gene Expression Profiling, Liquid Biopsy, Receptor Protein-Tyrosine Kinases, General Chemistry, Microarray Analysis, Programmed Cell Death 1 Ligand 2 Protein, medicine.disease, Axl Receptor Tyrosine Kinase, Immune checkpoint, Pleural Effusion, Malignant, 030104 developmental biology, Cancer research, lcsh:Q, business, Non-small-cell lung cancer, Cytometry |
| الوصف: | Accurate prediction of chemo- or targeted therapy responses for patients with similar driver oncogenes through a simple and least-invasive assay represents an unmet need in the clinical diagnosis of non-small cell lung cancer. Using a single-cell on-chip metabolic cytometry and fluorescent metabolic probes, we show metabolic phenotyping on the rare disseminated tumor cells in pleural effusions across a panel of 32 lung adenocarcinoma patients. Our results reveal extensive metabolic heterogeneity of tumor cells that differentially engage in glycolysis and mitochondrial oxidation. The cell number ratio of the two metabolic phenotypes is found to be predictive for patient therapy response, physiological performance, and survival. Transcriptome analysis reveals that the glycolytic phenotype is associated with mesenchymal-like cell state with elevated expression of the resistant-leading receptor tyrosine kinase AXL and immune checkpoint ligands. Drug targeting AXL induces a significant cell killing in the glycolytic cells without affecting the cells with active mitochondrial oxidation. Non-invasive methods to predict treatment response are urgently needed. Here in lung cancer, the authors develop a single-cell on-chip cytometry method to metabolically phenotype disseminated tumor cells, revealing metabolic heterogeneity and predictors of therapy response and survival. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f2a2ec472bb45bd704b980482fcddd5Test https://doaj.org/article/fc6306e74458427db8cad26bd5b3ccb6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6f2a2ec472bb45bd704b980482fcddd5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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