触珠蛋白表型：恶性胸膜间皮瘤的种系危险因素？病例对照研究

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-04-14 DOI:10.1016/j.cca.2025.120309

Kevin Lamote , Sigurd Delanghe , Marijn M. Speeckaert , Jan P. van Meerbeeck , Joris R. Delanghe

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引用次数: 0

摘要

目的恶性胸膜间皮瘤（MPM）的发病机制与石棉引起的慢性炎症、氧化剂形成、溶血和随后的血红蛋白（Hb）释放有关，从而加剧氧化损伤。粘连珠蛋白（Hp）作为一种主要的抗氧化剂，通过结合游离Hb来防止其有害影响。依赖于hp表型，这种络合可以是发散的，导致在石棉直接诱导或炎症细胞释放的活性氧（ROS）之上额外形成活性氧（ROS）。为了确定hp表型是MPM的一个危险因素，本病例对照研究比较了MPM患者与无症状的前职业性石棉暴露者（AEx）和来自欧洲人群的对照组的hp表型分布。材料与方法采用淀粉凝胶电泳对118例MPM患者和96例AEx患者的血清进行了shp表型分析。比较918名健康对照者Hp表型（Hp 1-1、Hp 2-1和Hp 2-2）和等位基因（Hp1、Hp2）的频率。结果与AEx患者（P = 0.001）和健康对照组（P = 0.005）相比，MPM患者的Hp - 1表型过高。与其他表型相比，AEx受试者的Hp 1-1表型发生MPM的相对风险为3.05(1.47-6.34)，健康对照组为1.74（1.19-2.54）。结论Hp- 1表型在MPM发病机制中起重要作用，Hp- 1表型的人更容易发生MPM。除了石棉引起的自由基形成，这一发现证实了氧化应激在癌症发展中的作用。

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Haptoglobin phenotype: A germline risk factor for malignant pleural mesothelioma? A case-control study

Purpose

The pathogenesis of malignant pleural mesothelioma (MPM) is linked to asbestos-induced chronic inflammation, oxidant formation, hemolysis and subsequent hemoglobin (Hb) release, potentiating oxidative injury. Haptoglobin (Hp) serves as a major antioxidant by binding free Hb in order to prevent its harmful effects. Dependent on the Hp-phenotype, this complexing can be divergent, leading to additional formation of reactive oxygen species (ROS) above those directly induced by asbestos or released by inflammatory cells. In order to determine the Hp-phenotype as a risk factor in MPM, this case-control study compared the Hp-phenotype distribution in MPM patients with asymptomatic persons with former occupational asbestos exposure (AEx) and controls from a European population.

Materials and Methods

Hp-phenotyping was done on serum samples of 118 MPM patients and 96 AEx subjects by starch gel electrophoresis. The frequencies of Hp phenotypes (Hp 1–1, Hp 2–1 and Hp 2–2) and alleles (Hp¹, Hp²) were compared with those from 918 healthy control subjects.

Results

The Hp 1–1 phenotype was overrepresented in MPM patients compared to AEx persons (P = 0.001) and healthy controls (P = 0.005). The relative risk for developing MPM when having the Hp 1–1 phenotype was 3.05 (1.47–6.34) for AEx subjects and 1.74 (1.19–2.54) for healthy controls compared to other phenotypes.

Conclusion

Our results indicate an important role of the Hp-phenotype in MPM pathogenesis suggesting that Hp 1–1 phenotypic persons are more prone for MPM development. Apart from the asbestos-induced radical formation, this finding confirms the role of oxidative stress in cancer development.

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.