气候变化领域集成服务门户(CCPortal): Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients

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DOI	10.1073/pnas.2012228118
	Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients
	Yang L.; Yan X.; Chen J.; Zhan Q.; Hua Y.; Xu S.; Li Z.; Wang Z.; Dong Y.; Zuo D.; Xue M.; Tang Y.; Herschman H.R.; Lu S.; Shi Q.; Wei W.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches despite the aggressive nature of NSCLC. Here, we demonstrate hexokinase-2 (HK2) as a metabolic function- associated marker for the detection of CTCs. In 59 NSCLC patients bearing cytokeratin-positive (CKpos) primary tumors, HK2 enables resolving cytokeratin-negative (HK2high/CKneg) CTCs as a prevalent population in about half of the peripheral blood samples with positive CTC counts. However, HK2high/CKnegtumor cells are a minority population in pleural effusions and cerebrospinal fluids. Singlecell analysis shows that HK2high/CKnegCTCs exhibit smaller sizes but consistent copy number variation profiles comparedwith CKposcounterparts. Single-cell transcriptome profiling reveals that CK expression levels of CTCs are independent of their epithelial-to-mesenchymal transition (EMT) status, challenging the long-standing association between CK expression and EMT. HK2high/CKnegCTCs display metastasis and EGFR inhibitor resistance-related molecular signatures and are selectively enriched in patientswith EGFRL858R driver oncogene mutation as opposed to EGFR19Del, which is more frequently found in patients with prevalent CKposCTCs in the blood. Consistently, treatment-naïve patients with a larger number or proportion of HK2high/CKnegCTCs in the blood exhibit poor therapy response and shorter progression-free survival. Collectively, our approach resolvesamore complete spectrum of CTCs in NSCLC that can potentially be exploited to identify patient prognosis before therapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Circulating tumor cells; Hexokinase-2; Liquid biopsy; Non-small cell lung cancer; Single-cell sequencing
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180237
作者单位	Department of Orthopedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; Institute for Systems Biology, Seattle, WA 98109, United States; Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China; Department of Oncology, Huashan Hospital, Fudan University, Shanghai, 200040, China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States; Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer (SMHC), Minhang Hospital, Fudan University, Shanghai, 201199, China
推荐引用方式 GB/T 7714	Yang L.,Yan X.,Chen J.,et al. Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients[J],2021,118(11).
APA	Yang L..,Yan X..,Chen J..,Zhan Q..,Hua Y..,...&Wei W..(2021).Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Yang L.,et al."Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).