整合组学特征分析揭示非小细胞肺癌患者经热消融治疗后癌症指标降低和炎症因子升高。

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

机构信息

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti South Road, Beijing, 100020, Chaoyang District, China.

Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

出版信息

Respir Res. 2024 Aug 14;25(1):309. doi: 10.1186/s12931-024-02917-9.

DOI:10.1186/s12931-024-02917-9

PMID:39143582

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11325606/

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.

摘要

背景

热消融是治疗非小细胞肺癌（NSCLC）的一种微创治疗方法。除了直接导致肿瘤细胞立即损伤外，热消融对内部微环境的影响尚不清楚。本研究旨在探讨热消融对 NSCLC 患者血浆内部环境的影响。

方法

从 48 例 NSCLC（消融前[LC]和消融后[LC-T]）患者和 32 例健康对照（HC）中收集了 128 个血浆样本。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 HC 相比，LC 患者表现出 58 个差异表达蛋白（DEPs）和 479 个差异表达代谢物（DEMs），这些蛋白可能参与肿瘤的进展和转移。此外，在 HC、LC 和 LC-T 组之间还鉴定出 75 个 DEP。LC 组中 48 个高表达 DEP（如程序性死亡配体 1 [PD-L1]）在热消融后下调。这些 DEP 对血管生成、免疫检查点阻断和促肿瘤趋化作用等途径有显著影响。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相关。相反，热消融后发现 19 个升高的蛋白（如白细胞介素[IL]-6）。这些蛋白主要与炎症反应途径（NF-κB 信号和肿瘤坏死因子信号）和免疫细胞激活相关。