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评估肺癌患者免疫系统检查点选定生物标志物的循环水平。

Assessment of the circulating levels of immune system checkpoint selected biomarkers in patients with lung cancer.

机构信息

Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614535, Tehran, Iran.

Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Rep. 2024 Oct 3;51(1):1036. doi: 10.1007/s11033-024-09971-y.

DOI:10.1007/s11033-024-09971-y
PMID:39361074
Abstract

BACKGROUND

Lung cancer is recognized as one of the leading causes of cancer-related deaths globally, with a significant increase in incidence and intricate pathogenic mechanisms. This study examines the expression profiles of Programmed Cell Death Protein 1 (PD-1), PD-1 ligand (PDL-1), β-catenin, CD44, interleukin 6 (IL-6), and interleukin 10 (IL-10), as well as their correlations with the clinic-pathological features and diagnostic significance in lung cancer patients.

METHODS AND RESULTS

The research involved lung cancer patients exhibiting various pathological characteristics, alongside demographically matched healthy controls. The expression levels of PD-1, PDL-1, β-catenin, and CD44 were analyzed using Real-Time PCR, while circulating levels of IL-6 and IL-10 were assessed through ELISA assays. This investigation focused on peripheral blood mononuclear cells (PBMC) to evaluate these factors non-invasively. Findings indicated that levels of PD-1, PDL-1, and CD44 were significantly elevated in patients compared to controls, which coincided with a decrease in β-catenin levels. Additionally, a concurrent rise in IL-6 and IL-10, both pro-inflammatory cytokines, was observed in patients, suggesting a potential regulatory role for these cytokines on the PD-1/PDL-1 axis, which may help tumors evade immune system checkpoints. The predictive value of these factors concerning lung tumors and metastasis was significant (Regression analysis). Furthermore, these markers demonstrated diagnostic potential in differentiating between patients and healthy controls, as well as between individuals with metastatic and non-metastatic tumors (ROC curve analysis).

CONCLUSIONS

This study provides insights into the expression profiles of PD-1/PDL-1 immune system checkpoints and their regulatory factors in lung cancer, potentially paving the way for new therapeutic and diagnostic approaches.

摘要

背景

肺癌是全球癌症相关死亡的主要原因之一,其发病率显著增加,发病机制复杂。本研究探讨了程序性细胞死亡蛋白 1(PD-1)、PD-1 配体(PDL-1)、β-连环蛋白、CD44、白细胞介素 6(IL-6)和白细胞介素 10(IL-10)的表达谱,以及它们与肺癌患者临床病理特征的相关性及其诊断意义。

方法和结果

本研究涉及具有不同病理特征的肺癌患者和年龄匹配的健康对照者。采用 Real-Time PCR 分析 PD-1、PDL-1、β-连环蛋白和 CD44 的表达水平,采用 ELISA 法检测循环 IL-6 和 IL-10 水平。本研究聚焦于外周血单核细胞(PBMC),以无创性评估这些因子。研究结果表明,与对照组相比,患者 PD-1、PDL-1 和 CD44 水平显著升高,而β-连环蛋白水平降低。此外,患者体内促炎细胞因子 IL-6 和 IL-10 同时升高,提示这些细胞因子可能对 PD-1/PDL-1 轴具有潜在的调节作用,有助于肿瘤逃避免疫系统的检查点。这些因素对肺肿瘤和转移的预测价值具有显著意义(回归分析)。此外,这些标志物在区分患者与健康对照者、转移性与非转移性肿瘤患者方面具有诊断潜力(ROC 曲线分析)。

结论

本研究深入了解了肺癌中 PD-1/PDL-1 免疫系统检查点及其调节因子的表达谱,为新的治疗和诊断方法提供了思路。

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