评价 EGFR 外显子 19 747-750 缺失突变和血浆氨基酸谱在肺癌发展中的作用。

Evaluation of the role of EGFR exon 19 747-750 deletion mutation and plasma amino acid profile in the development of lung cancer.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.

Department of Cardiothoracic Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt.

出版信息

Mol Biol Rep. 2024 Oct 4;51(1):1039. doi: 10.1007/s11033-024-09941-4.

DOI:10.1007/s11033-024-09941-4

PMID:39367097

Abstract

BACKGROUND

Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor's status. The present study is designed to detect the relation between the EGFR exon 19 747-750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer.

METHODS

The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the EGFR exon 19 747-750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile.

RESULTS

Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis.

CONCLUSION

Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.

摘要

背景

肺癌（LC）是世界上最常见的癌症形式。在参与细胞分化和增殖的蛋白质中，表皮生长因子受体（EGFR）是最重要的蛋白质之一。氨基酸在细胞生理中作为代谢调节剂发挥着至关重要的作用。液体活检的优点在于其非侵入性、易于采集以及能够描绘整个肿瘤的状态。本研究旨在检测 EGFR 外显子 19 747-750 缺失突变与肺癌之间的关系，并研究不同组织病理学类型和阶段的肺癌患者血浆游离氨基酸（PFAA）模式的改变，作为肺癌早期检测的生物标志物。

方法

研究样本包括 60 例肺癌患者和 60 名年龄和性别匹配的健康个体作为对照组。聚合酶链反应和限制性片段长度多态性（PCR-RFLP）用于检测 EGFR 外显子 19 747-750 缺失突变，AA 分析仪用于定量血浆游离氨基酸（PFAA）谱。

结果

与对照组相比，LC 患者有三种氨基酸水平显著升高，有十五种氨基酸水平显著降低。十三种氨基酸在 I 期和 II 期之间有显著差异。在肺癌组中，突变型 EGFR 外显子 19 缺失的病例百分比从对照组的 13.3%增加到 30%。在这种增加中，肺癌的组织学形式没有显著差异。突变型的缬氨酸和瓜氨酸血浆水平明显高于野生型。赖氨酸、组氨酸和蛋氨酸是多元分析中 LC 组的独立预测因子。