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
复制标题
基于液体活检的肺癌患者单细胞代谢表型分析，用于信息诊断
DOI：
10.1038/s41467-019-11808-3
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发表时间：
2019-08-26
影响因子：
16.6
通讯作者：
Shi, Qihui
中科院分区：
文献类型：
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作者：
Li, Ziming;Wang, Zhuo;Shi, Qihui
在非小细胞肺癌的临床诊断中，通过一种简单和最小创的方法准确预测具有相似驱动癌基因的患者的化疗或靶向治疗反应，是一个尚未得到满足的需求。使用单细胞芯片代谢细胞仪和荧光代谢探针，我们显示了32例肺腺癌患者胸腔积液中罕见的播散性肿瘤细胞的代谢表型。我们的结果揭示了肿瘤细胞广泛的代谢异质性，这些细胞不同地参与糖酵解和线粒体氧化。这两种代谢表型的细胞数量比率被发现可以预测患者的治疗反应、生理表现和生存。转录组分析表明，糖酵解表型与间充质样细胞状态相关，耐药领先受体酪氨酸激酶Axl和免疫检查点配体表达增加。靶向药物Axl在糖酵解细胞中诱导显着的细胞杀伤，而不影响线粒体氧化活跃的细胞。
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.