ERCC1 Which Affects Lipids Metabolism and Actin Dynamics in Coal Workers' Pneumoconiosis is a Candidate Biomarker for Early Warning and Diagnosis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Sep 16

PMID 39283905

Authors

Hao Deng

Yan Chen

Mali Wu

Tao Zhang

Affiliations

Soon will be listed here.

Abstract

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.

References

Yu T, Xue P, Cui S, Zhang L, Zhang G, Xiao M . Rs3212986 polymorphism, a possible biomarker to predict smoking-related lung cancer, alters DNA repair capacity via regulating ERCC1 expression. Cancer Med. 2018; 7(12):6317-6330. PMC: 6308093. DOI: 10.1002/cam4.1842. View

Huerta Guevara A, McGowan S, Kazantzis M, Stallons T, Sano T, Mulder N . Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1 mice. Metabolism. 2021; 117:154711. PMC: 8625516. DOI: 10.1016/j.metabol.2021.154711. View

Ji X, Hou Z, Wang T, Jin K, Fan J, Luo C . Polymorphisms in inflammasome genes and risk of coal workers' pneumoconiosis in a Chinese population. PLoS One. 2012; 7(10):e47949. PMC: 3478280. DOI: 10.1371/journal.pone.0047949. View

Chair S, Chan J, Law B, Waye M, Chien W . Genetic susceptibility in pneumoconiosis in China: a systematic review. Int Arch Occup Environ Health. 2022; 96(1):45-56. DOI: 10.1007/s00420-022-01893-1. View

Hou Z, Zhang X, Gao Y, Geng J, Jiang Y, Dai H . Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study. Pharmgenomics Pers Med. 2023; 16:537-549. PMC: 10241210. DOI: 10.2147/PGPM.S409644. View

Poli G, Schaur R, Siems W, Leonarduzzi G . 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Med Res Rev. 2007; 28(4):569-631. DOI: 10.1002/med.20117. View

Park S, Seo Y . Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle. Int J Mol Sci. 2020; 21(6). PMC: 7139950. DOI: 10.3390/ijms21061949. View

Li J, Yin P, Wang H, Wang L, You J, Liu J . The burden of pneumoconiosis in China: an analysis from the Global Burden of Disease Study 2019. BMC Public Health. 2022; 22(1):1114. PMC: 9166455. DOI: 10.1186/s12889-022-13541-x. View

Kim E, Ahuja A, Kim M, Cho J . DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function. Cells. 2021; 10(2). PMC: 7926996. DOI: 10.3390/cells10020461. View

10.

Weng S, Wang L, Rong Y, Liu Y, Wang X, Guan H . Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study. PLoS One. 2015; 10(10):e0140952. PMC: 4619690. DOI: 10.1371/journal.pone.0140952. View

11.

Zhao W, Wang L, Wang Y, Yuan H, Zhao M, Lian H . Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis. Int J Mol Sci. 2023; 24(10). PMC: 10218114. DOI: 10.3390/ijms24108749. View

12.

Song M, Wang J, Sun Y, Han Z, Zhou Y, Liu Y . Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages. Acta Pharmacol Sin. 2021; 43(5):1274-1284. PMC: 9061833. DOI: 10.1038/s41401-021-00693-6. View

13.

Xu Y, Li H, Hedmer M, Hossain M, Tinnerberg H, Broberg K . Occupational exposure to particles and mitochondrial DNA - relevance for blood pressure. Environ Health. 2017; 16(1):22. PMC: 5343309. DOI: 10.1186/s12940-017-0234-4. View

14.

Perez-Ramirez C, Canadas-Garre M, Alnatsha A, Villar E, Valdivia-Bautista J, Faus-Dader M . Pharmacogenetics of platinum-based chemotherapy: impact of DNA repair and folate metabolism gene polymorphisms on prognosis of non-small cell lung cancer patients. Pharmacogenomics J. 2018; 19(2):164-177. DOI: 10.1038/s41397-018-0014-8. View

15.

Deng H, Zhang T, Wu M, Yang G, Chen Y, Liang Y . [Expression and functional SNP loci screen of from coal worker's pneumoconiosis]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022; 40(2):103-108. DOI: 10.3760/cma.j.cn121094-20201019-00590. View

16.

London R . XRCC1 - Strategies for coordinating and assembling a versatile DNA damage response. DNA Repair (Amst). 2020; 93:102917. PMC: 7587305. DOI: 10.1016/j.dnarep.2020.102917. View

17.

Isla D, Sarries C, Rosell R, Alonso G, Domine M, Taron M . Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol. 2004; 15(8):1194-203. DOI: 10.1093/annonc/mdh319. View

18.

Kell L, Simon A, Alsaleh G, Cox L . The central role of DNA damage in immunosenescence. Front Aging. 2023; 4:1202152. PMC: 10351018. DOI: 10.3389/fragi.2023.1202152. View

19.

Melchionna R, Trono P, Tocci A, Nistico P . Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links. Biomolecules. 2021; 11(2). PMC: 7926735. DOI: 10.3390/biom11020336. View

20.

Rayens N, Rayens E, Tighe R . Co-occurrence of pneumoconiosis with COPD, pneumonia and lung cancer. Occup Med (Lond). 2022; 72(8):527-533. DOI: 10.1093/occmed/kqac079. View