Integrated omics characterization reveals reduced cancer indicators and elevated inflammatory factors after thermal ablation in non-small cell lung cancer patients.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2024-08-14 DOI:10.1186/s12931-024-02917-9

Xinglu Zhang, Shuai Shao, Nan Song, Baolu Yang, Fengjiao Liu, Zhaohui Tong, Feng Wang, Jieqiong Li

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引用次数: 0

Abstract

Background: Thermal ablation is a minimally invasive treatment for non-small cell lung cancer (NSCLC). Aside from causing an immediate direct tumour cell injury, the effects of thermal ablation on the internal microenvironment are unknown. This study aimed to investigate the effects of thermal ablation on the plasma internal environment in patients with NSCLC.

Methods: 128 plasma samples were collected from 48 NSCLC (pre [LC] and after thermal ablation [LC-T]) patients and 32 healthy controls (HCs). Olink proteomics and metabolomics were utilized to construct an integrated landscape of the cancer-related immune and inflammatory responses after ablation.

Results: Compared with HCs, LC patients exhibited 58 differentially expressed proteins (DEPs) and 479 differentially expressed metabolites (DEMs), which might participate in tumour progression and metastasis. Moreover, 75 DEPs were identified among the HC, LC, and LC-T groups. Forty-eight highly expressed DEPs (eg, programmed death-ligand 1 [PD-L1]) in the LC group were found to be downregulated after thermal ablation. These DEPs had significant impacts on pathways such as angiogenesis, immune checkpoint blockade, and pro-tumour chemotaxis. Metabolites involved in tumour cell survival were associated with these proteins at the expression and functional levels. In contrast, 19 elevated proteins (eg, interleukin [IL]-6) were identified after thermal ablation. These proteins were mainly associated with inflammatory response pathways (NF-κB signalling and tumour necrosis factor signalling) and immune cell activation.

Conclusions: Thermal ablation-induced changes in the host plasma microenvironment contribute to anti-tumour immunity in NSCLC, offering new insights into tumour ablation combined with immunotherapy. Trial registration This study was registered on the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html ). ID: ChiCTR2300076517. Registration Date: 2023-10-11.

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综合全息表征显示，非小细胞肺癌患者热消融后癌症指标降低，炎症因子升高。

背景：热消融是一种治疗非小细胞肺癌（NSCLC）的微创疗法。除了对肿瘤细胞造成直接伤害外，热消融对肿瘤内部微环境的影响尚不清楚。本研究旨在调查热消融对 NSCLC 患者血浆内部环境的影响。方法：从 48 名 NSCLC（热消融前 [LC] 和热消融后 [LC-T]）患者和 32 名健康对照组（HCs）中收集 128 份血浆样本。利用Olink蛋白质组学和代谢组学构建了消融后癌症相关免疫和炎症反应的综合图谱：结果：与对照组相比，LC 患者表现出 58 种差异表达蛋白（DEPs）和 479 种差异表达代谢物（DEMs），这些蛋白和代谢物可能参与了肿瘤的进展和转移。此外，在 HC 组、LC 组和 LC-T 组中发现了 75 种 DEPs。发现热消融后，LC 组中 48 个高表达的 DEPs（如程序性死亡配体 1 [PD-L1]）被下调。这些DEPs对血管生成、免疫检查点阻断和促肿瘤趋化等通路有重大影响。涉及肿瘤细胞存活的代谢物在表达和功能水平上与这些蛋白质相关。相比之下，热消融后发现了 19 种升高的蛋白质（如白细胞介素 [IL]-6）。这些蛋白质主要与炎症反应途径（NF-κB 信号传导和肿瘤坏死因子信号传导）和免疫细胞活化有关：热消融诱导的宿主血浆微环境变化有助于NSCLC的抗肿瘤免疫，为肿瘤消融与免疫疗法的结合提供了新的见解。试验注册本研究已在中国临床试验注册中心 ( https://www.chictr.org.cn/index.html ) 注册。ID：ChiCTR2300076517.注册日期：2023-10-11。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.