Deng Hao, Chen Yan, Wu Mali, Zhang Tao
Department of Occupational Diseases, Guiyang Public Health Clinical Center, Guiyang, GuiZhou, China.
Institute of Public Health, Guizhou CDC, Guiyang, GuiZhou, China.
PLoS One. 2024 Sep 16;19(9):e0308082. doi: 10.1371/journal.pone.0308082. eCollection 2024.
The single-nucleotide polymorphisms of genes related to DNA damage repair and inflammasomes and mutated gene expression in coal workers' pneumoconiosis (CWP) were analysed to identify the risk factors of CWP and potential biomarkers for early warning and diagnosis. Further, mutated gene pathways were analysed based on proteome and metabolome. Han Chinese male subjects were randomly selected and divided into 4 or 5 groups according to the process of CWP. MassARRAY was used to sequence single-nucleotide polymorphism genotypes. Mutated gene expression in plasma was tested using enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and receiver operating characteristic curves (ROC) were calculated. The serum different proteins and metabolites were identified by Ultra Performance Liquid Chromatography Quadrupole time of flight/Mass Spectrum (UPLC-Q-TOF/MS) and analysed using bioinformation software. As CWP progressed, the CC and CA genotypes of ERCC1 rs3212986 decreased and increased significantly, respectively. AA (OR = 3.016) and CA (OR = 2.130) genotypes were identified as risk factors for stage II. ERCC1 significantly decreased in processing of CWP. The cutoff value of ERCC1 was 5.265 pg/ml, with a sensitivity of 90.0% and specificity of 86.7%. ERCC1 had an indirect interaction with activator protein-1 and insulin and its pathways were mainly made with molecules related to lipid metabolism and actin dynamics. ERCC1 is a candidate biomarker for detection and precise intervention in CWP. If it reaches the threshold, workers will change other jobs in time and will not develop and diagnose as pneumoconiosis and will help the employers spend less money. Meanwhile, the signal molecules of ERCC1 pathway could be as a candidate target for drug discovery.
分析了与DNA损伤修复和炎性小体相关基因的单核苷酸多态性以及煤工尘肺（CWP）中的突变基因表达，以确定CWP的危险因素和早期预警与诊断的潜在生物标志物。此外，基于蛋白质组和代谢组分析了突变基因途径。随机选择汉族男性受试者，并根据CWP的病程分为4组或5组。使用MassARRAY对单核苷酸多态性基因型进行测序。采用酶联免疫吸附测定（ELISA）检测血浆中突变基因的表达。计算比值比（OR）和受试者工作特征曲线（ROC）。通过超高效液相色谱四极杆飞行时间质谱（UPLC-Q-TOF/MS）鉴定血清中的不同蛋白质和代谢物，并使用生物信息软件进行分析。随着CWP的进展，ERCC1 rs3212986的CC和CA基因型分别显著降低和升高。AA（OR = 3.016）和CA（OR = 2.130）基因型被确定为II期的危险因素。在CWP进展过程中ERCC1显著降低。ERCC1的临界值为5.265 pg/ml，敏感性为90.0%，特异性为86.7%。ERCC1与激活蛋白-1和胰岛素存在间接相互作用，其途径主要与脂质代谢和肌动蛋白动力学相关分子有关。ERCC1是CWP检测和精准干预的候选生物标志物。如果达到阈值，工人将及时更换其他工作，不会发展和诊断为尘肺病，这将有助于雇主节省开支。同时，ERCC1途径的信号分子可作为药物研发的候选靶点。
