SCI
11 September 2019
Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics
Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics
Li Ziming,Wang Zhuo,Tang Yin et al. Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics.[J] .Nat Commun, 2019, 10: 3856.
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.
使用单细胞片上代谢细胞计数和荧光代谢探针，我们显示在一组32名肺腺癌患者的胸腔积液中罕见的播散性肿瘤细胞的代谢表型。我们的研究结果揭示了肿瘤细胞的广泛代谢异质性，差异性地参与糖酵解和线粒体氧化。两种代谢表型的细胞数比可预测患者治疗反应，生理学表现和存活。转录组分析显示，糖酵解表型与间充质样细胞状态相关，其中抗性主导受体酪氨酸激酶AXL和免疫检查点配体的表达升高。药物靶向AXL在糖酵解细胞中诱导显着的细胞杀伤而不影响具有活性线粒体氧化的细胞。
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