fgl1介导的T1期非小细胞肺癌淋巴结转移:靶向治疗。

IF 13.5 1区 医学 Q1 HEMATOLOGY
Xi-Yang Tang, Run-Ze Zhang, Zhi-Bo Feng, Yu-Long Zhou, Wei-Guang Du, Chen Shu, Yang Shen, Meng-Chao Li, Jun-Chao Cai, Xiao-Long Yan, Nan Ma, Jin-Bo Zhao
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引用次数: 0

摘要

背景:大约30%的T1期非小细胞肺癌(NSCLC)患者有纵隔(N2)淋巴结转移;然而,其潜在机制尚不清楚。方法:采用单细胞测序方法对T1期NSCLC中可能介导N2淋巴结转移的细胞进行鉴定。通过单细胞分析分析主要功能基因高纤维蛋白原样蛋白1 (FGL1)在该细胞亚群中的表达及功能。结合体外和体内实验进行转录组测序、代谢组测序和质谱分析,并使用shFGL1_AAV9和shFGL1_AAV6进行治疗性验证。结果:发现了一个以FGL1表达为特征的新细胞亚群(CCNE1(+)细胞)。FGL1的表达与该细胞亚群的出现一致,提示FGL1 +细胞介导T1 NSCLC N2淋巴结转移。质谱法结合转录测序和代谢组学研究显示,FGL1可能通过PI3K/AKT/HIF-1α途径影响NSCLC的糖酵解调节因子,并参与上皮-间质转化。进一步分析表明,FGL1促进肿瘤增殖、转移和淋巴管形成,最终诱导淋巴结转移。这在体内和体外得到了验证。FGL1敲低抑制了这些过程。最后,shFGL1_AAV9和shFGL1_AAV6被验证为体内敲除FGL1的新型靶向疗法,支持发现抑制NSCLC转移的新治疗靶点。结论:我们阐明了FGL1在NSCLC中的作用,提出FGL1在介导T1 NSCLC N2淋巴结管形成,建立转移通道中发挥了“屏蔽机割刀”的作用。这为新的fgl1靶向治疗策略提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FGL1-mediated lymph node metastasis in stage T1 non-small cell lung cancer: therapeutic targeting.

Background: Approximately 30% of patients with stage T1 non-small cell lung cancer (NSCLC) have mediastinal (N2) lymph node metastasis; however, the underlying mechanism remains unclear.

Methods: The cells likely mediating N2 lymph node metastasis in T1 NSCLC were identified by single-cell sequencing. The expression and function of the main functional gene high fibrinogen-like protein 1 (FGL1) in this cell subgroup were analyzed by single-cell analysis. Transcriptome sequencing, metabolome sequencing, and mass spectrometry combined with in vitro and in vivo experiments were conducted, and therapeutic validation was performed using shFGL1_AAV9 and shFGL1_AAV6.

Results: A novel cell subgroup characterized by FGL1 expression was identified (CCNE1(+) cells). FGL1 expression coincided with the appearance of this cell subgroup, suggesting that FGL1 + cells mediate T1 NSCLC N2 lymph node metastasis. Mass spectrometry combined with transcription sequencing and metabonomics revealed that FGL1 may affect glycolysis regulators and participate in epithelial-to-mesenchymal transition in NSCLC via the PI3K/AKT/HIF-1α pathway. Further analyses suggested that FGL1 promotes tumor proliferation, metastasis, and lymph tube formation, ultimately inducing lymph node metastasis. This was verified in vivo and in vitro. FGL1 knockdown inhibited these processes. Finally, shFGL1_AAV9 and shFGL1_AAV6 were verified as novel targeted therapies to knock down FGL1 in vivo, supporting the identification of new therapeutic targets to inhibit NSCLC metastasis.

Conclusion: We elucidated the role of FGL1 in NSCLC, proposing that FGL1 acts like a "shield machine cutter" in mediating T1 NSCLC N2 lymph node tube formation, creating metastasis channels. This provides the basis for novel FGL1-targeting treatment strategies.

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来源期刊
CiteScore
12.60
自引率
7.30%
发文量
97
审稿时长
6 weeks
期刊介绍: Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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