Altered Genes in Asbestose contamination
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 16 (2026),
1 January 2026
,
Page 1-11
https://doi.org/10.22037/ijmtfm.v16.51912
Abstract
Background: Today, many people have heard about the dangers of asbestos pollution. The use of asbestos has been banned in many countries. The only way to prevent asbestos pollution is to avoid breathing it in and coming into contact with it. The symptoms and damage caused by asbestos may not appear for years. Therefore, it is important to find changes in gene expression caused by asbestos pollution.
Methods: Initially, genes whose expression changes following asbestos exposure are extracted from relevant databases, such as GEO. From the gene expression data, genes that have changed significantly, as indicated by the adjusted p-value, are identified. Using undirected protein networks, these genes are entered into the internetwork structure. The formed network (interactome) is analyzed, and centrality indices are examined to determine central genes. Genes with higher centrality are selected. Gene-related biochemical pathways are extracted from the KEGG database. Related genes and biochemical pathways are validated through a literature review.
Results: Network analysis of genes altered by asbestos exposure identified key hub and bottleneck genes. From a set of 96 differentially expressed genes, three high-connectivity hubs (GAPDH, ACTB, IL6) and five critical bottlenecks (GAPDH, RPS27A, ACTB, VTN, APP) were prioritized. The consensus genes GAPDH and ACTB were found in both categories, underscoring their potentially pivotal role in the asbestos-response network.
Conclusion: This systems biology analysis identifies central molecular targets, particularly GAPDH and ACTB, within the asbestos-induced gene network. These findings provide a prioritized framework for future research into targeted genetic and therapeutic strategies aimed at mitigating asbestos-related pathologies.
- Asbestos
- Lung cancer
- Asbestosis
- Genes
How to Cite
References
[1] Durczak K, Pyzalski M, Brylewski T, Juszczyk M, Leśniak A, Libura M, et al. Modern Methods of Asbestos Waste Management as Innovative Solutions for Recycling and Sustainable Cement Production. Sustainability. 2024;16(20):8798. [DOI: 10.3390/su16208798]
[2] Olsson A, Kovalevskiy EV, Talibov M, Moissonnier M, Byrnes G, Bouaoun L, et al. Tobacco smoking among chrysotile asbestos workers in Asbest in the Russian Federation. Occup Environ Med. 2020;77(9):623–7. [DOI: 10.1136/oemed-2019-106263]
[3] Schüz J, Kovalevskiy E, Olsson A, Moissonnier M, Ostroumova E, Ferro G, et al. Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study). J Natl Cancer Inst. 2024;116(6):866–75. [DOI: 10.1093/jnci/djad262]
[4] Ospina D, Villegas VE, Rodríguez-Leguizamón G, Rondón-Lagos M. Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos. Cancer Manag Res. 2019;11:4997–5012. [DOI: 10.2147/cmar.S205723]
[5] Kovalevskiy EV, Schonfeld SJ, Feletto E, Moissonnier M, Kashanskiy SV, Bukhtiyarov IV, et al. Comparison of mortality in Asbest city and the Sverdlovsk region in the Russian Federation: 1997-2010. Environ Health. 2016;15:42. [DOI: 10.1186/s12940-016-0125-0]
[6] Köksal D, Bayiz H, Gülgösteren M, Başay N, Mutluay N, Boyacı E, et al. Recurrence of thymoma after 11 years presenting as diffuse pleural thickening. Tuberk Toraks. 2012;60(1):62–5. [DOI: 10.5578/tt.1993]
[7] Schüz J, Bukhtiyarov I, Olsson A, Moissonnier M, Ostroumova E, Feletto E, et al. Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study. PLoS One. 2020;15(7):e0236475. [DOI: 10.1371/journal.pone.0236475]
[8] Gelmi MC, de Ru AH, van Veelen PA, Tjokrodirijo RTN, Stern MH, Houy A, et al. Protein and mRNA Expression in Uveal Melanoma Cell Lines Are Related to GNA and BAP1 Mutation Status. Invest Ophthalmol Vis Sci. 2024;65(8):37. [DOI: 10.1167/iovs.65.8.37]
[9] Sekido Y, Sato T. NF2 alteration in mesothelioma. Frontiers in Toxicology. 2023;Volume 5 - 2023. [DOI: 10.3389/ftox.2023.1161995]
[10] Barton C, Al Achkar M, Blender JA, Farmen SH, Hall RB, Konidari AM, et al. Patient-led advocacy in ALK-positive lung cancer. Transl Lung Cancer Res. 2023;12(6):1303–19. [DOI: 10.21037/tlcr-22-713]
[11] Kreuger IZM, Slieker RC, van Groningen T, van Doorn R. Therapeutic Strategies for Targeting CDKN2A Loss in Melanoma. J Invest Dermatol. 2023;143(1):18–25.e1. [DOI: 10.1016/j.jid.2022.07.016]
[12] Uguen M, Dewitte JD, Marcorelles P, Loddé B, Pougnet R, Saliou P, et al. Asbestos-related lung cancers: A retrospective clinical and pathological study. Mol Clin Oncol. 2017;7(1):135–9. [DOI: 10.3892/mco.2017.1277]
[13] Feletto E, Kovalevskiy EV, Schonfeld SJ, Moissonnier M, Olsson A, Kashanskiy SV, et al. Developing a company-specific job exposure matrix for the Asbest Chrysotile Cohort Study. Occup Environ Med. 2022;79(5):339–46. [DOI: 10.1136/oemed-2021-107438]
[14] Wadowski B, De Rienzo A, Bueno R. The Molecular Basis of Malignant Pleural Mesothelioma. Thorac Surg Clin. 2020;30(4):383–93. [DOI: 10.1016/j.thorsurg.2020.08.005]
[15] Schonfeld SJ, Kovalevskiy EV, Feletto E, Bukhtiyarov IV, Kashanskiy SV, Moissonier M, et al. Temporal Trends in Airborne Dust Concentrations at a Large Chrysotile Mine and its Asbestos-enrichment Factories in the Russian Federation During 1951-2001. Ann Work Expo Health. 2017;61(7):797–808. [DOI: 10.1093/annweh/wxx051]
[16] Baur X. Asbestos-Related Disorders in Germany: Background, Politics, Incidence, Diagnostics and Compensation. Int J Environ Res Public Health. 2018;15(1). [DOI: 10.3390/ijerph15010143]
[17] Hong QY, Wu GM, Qian GS, Hu CP, Zhou JY, Chen LA, et al. Prevention and management of lung cancer in China. Cancer. 2015;121 Suppl 17:3080–8. [DOI: 10.1002/cncr.29584]
[18] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. [DOI: 10.3322/caac.21332]
[19] Redman KL, Rechsteiner M. Identification of the long ubiquitin extension as ribosomal protein S27a. Nature. 1989;338(6214):438–40. [DOI: 10.1038/338438a0]
[20] Li H, Zhang H, Huang G, Bing Z, Xu D, Liu J, et al. Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells. J Exp Clin Cancer Res. 2022;41(1):33. [DOI: 10.1186/s13046-021-02230-z]
[21] Su Y, Kondrikov D, Block ER. Beta-actin: a regulator of NOS-3. Sci STKE. 2007;2007(404):pe52. [DOI: 10.1126/stke.4042007pe52]
[22] Atzmony L, Ugwu N, Zaki TD, Antaya RJ, Choate KA. Post-zygotic ACTB mutations underlie congenital smooth muscle hamartomas. J Cutan Pathol. 2020;47(8):681–5. [DOI: 10.1111/cup.13683]
[23] MacPherson M, Westbom C, Kogan H, Shukla A. Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro. Histochem Cell Biol. 2017;147(5):595–604. [DOI: 10.1007/s00418-016-1530-8]
[24] Tarasova EK, Pavlova EN, Rybalkina EY, Scherbakova EA, Tarasov RV, Erokhina MV. Validation of Housekeeping Genes for Normalizing RNA Expression in Real-Time PCR in Tuberculomas and Peripheral Blood Mononuclear Cells for Pulmonary Tuberculosis Patients. International Journal of Molecular Sciences. 2025;26(22):11219. [DOI: 10.3390/ijms262211219]
[25] Ruzha Y, Ni J, Quan Z, Li H, Qing H. Role of Vitronectin and Its Receptors in Neuronal Function and Neurodegenerative Diseases. Int J Mol Sci. 2022;23(20). [DOI:10.3390/ijms232012387]
[26] Cheng YY, Rath EM, Linton A, Yuen ML, Takahashi K, Lee K. The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer. Lung Cancer (Auckl). 2020;11:1–11. [DOI: 10.2147/lctt.S186843]
[27] Strope TA, Wilkins HM. Amyloid precursor protein and mitochondria. Curr Opin Neurobiol. 2023;78:102651. [DOI: 10.1016/j.conb.2022.102651]
[28] Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. [DOI: 10.1101/cshperspect.a016295]
[29] Pestechian N, Rasekh H, Rostami-Nejad M, Yousofi HA, Hosseini-Safa A. Molecular identification of Giardia lamblia; is there any correlation between diarrhea and genotyping in Iranian population? Gastroenterol Hepatol Bed Bench. 2014;7(3):168–72. [Link]
[30] Tatton WG, Chalmers-Redman RM, Elstner M, Leesch W, Jagodzinski FB, Stupak DP, et al. Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. J Neural Transm Suppl. 2000(60):77–100. [DOI: 10.1007/978-3-7091-6301-6_5]
[31] Özkan DT, Sarper N, Akar N. Genetic analysis of afibrinogenemia and hypofibrinogenemia: novel mutations in the FGB gene in the Turkish population. Acta Haematologica. 2020;143(6):529–32. [DOI: 10.1159/000505174]
[32] Eastham MJ, Pelava A, Wells GR, Watkins NJ, Schneider C. RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling. Biomolecules. 2023;13(6). [DOI: 10.3390/biom13060898]
[33] Zielonka TM. Angiogenesis in interstitial lung diseases. Advances in Respiratory Medicine. 2009;77(1):52–60. [DOI: 10.5603/ARM.27845]
[34] Parker F, Baboolal TG, Peckham M. Actin Mutations and Their Role in Disease. Int J Mol Sci. 2020;21(9). [DOI: 10.3390/ijms21093371]
[35] Kallio SP, Jakkula E, Purcell S, Suvela M, Koivisto K, Tienari PJ, et al. Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS. Human molecular genetics. 2009;18(9):1670–83. [DOI: 10.1093/hmg/ddp073]
[36] Wang Y, Xu J, Chen J, Fan X, Zhang Y, Yu W, et al. Promoter variants of VTN are associated with vascular disease. International journal of cardiology. 2013;168(1):163–8. [DOI: 10.1016/j.ijcard.2012.09.100]
[37] Rausz E, Szilágyi A, Nedoszytko B, Lange M, Niedoszytko M, Lautner‐Csorba O, et al. Comparative analysis of IL 6 and IL 6 receptor gene polymorphisms in mastocytosis. British journal of haematology. 2013;160(2):216–9. [DOI: 10.1111/bjh.12086]
[38] Soukupova J, Stastna B, Kanwal M, Hojny J, Zemankova P, Borecka M, et al. A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer. Cancer Med. 2024;13(16):e70103. [DOI: 10.1002/cam4.70103]
[39] Isenberg JS, Roberts DD. THBS1 (thrombospondin-1). Atlas of genetics and cytogenetics in oncology and haematology. 2020;24(8):291. [DOI: 10.4267/2042/70774]
[40] Góth L, Nagy T. Inherited catalase deficiency: is it benign or a factor in various age related disorders? Mutat Res. 2013;753(2):147–54. [DOI: 10.1016/j.mrrev.2013.08.002]
[41] Bibert S, Bratschi MW, Aboagye SY, Collinet E, Scherr N, Yeboah-Manu D, et al. Susceptibility to Mycobacterium ulcerans disease (Buruli ulcer) is associated with IFNG and iNOS gene polymorphisms. Frontiers in microbiology. 2017;8:1903. [DOI: 10.3389/fmicb.2017.01903]
[42] Tunesi S, Ferrante D, Mirabelli D, Andorno S, Betti M, Fiorito G, et al. Gene-asbestos interaction in malignant pleural mesothelioma susceptibility. Carcinogenesis. 2015;36(10):1129–35. [DOI: 10.1093/carcin/bgv097]
[43] Herzberg C, Friedrich A, Averhoff B. comB, a novel competence gene required for natural transformation of Acinetobacter sp. BD413: identification, characterization, and analysis of growth-phase-dependent regulation. Arch Microbiol. 2000;173(3):220–8. [DOI: 10.1007/s002039900134]
[44] Jung M, Sabat R, Krätzschmar J, Seidel H, Wolk K, Schönbein C, et al. Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy. European journal of immunology. 2004;34(2):481–93. [DOI: 10.1002/eji.200324323]
[45] Zheng Y, Fang Z, Xue Y, Zhang J, Zhu J, Gao R, et al. Specific gut microbiome signature predicts the early-stage lung cancer. Gut Microbes. 2020;11(4):1030–42. [DOI: 10.1080/19490976.2020.1737487]
[46] Columbres RCA, Chin Y, Pratti S, Quinn C, Gonzalez-Cuyar LF, Weiss M, et al. Novel variants in the VCP gene causing multisystem proteinopathy 1. Genes. 2023;14(3):676. [DOI: 10.3390/genes14030676]
[47] Wetsel R, Fleischer DT, Haviland D. Deficiency of the murine fifth complement component (C5). A 2-base pair gene deletion in a 5'-exon. Journal of Biological Chemistry. 1990;265(5):2435–40. [DOI: 10.1016/S0021-9258(19)39817-5]
[48] Shen B, Singh P, Liu R, Qiu J, Zheng L, Finger LD, et al. Multiple but dissectible functions of FEN‐1 nucleases in nucleic acid processing, genome stability and diseases. Bioessays. 2005;27(7):717–29. [DOI: 10.1002/bies.20255]
[49] Bidault G, Vatier C, Capeau J, Vigouroux C, Béréziat V. LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations. Biochem Soc Trans. 2011;39(6):1752–7. [DOI: 10.1042/bst20110675]
[50] Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683–92. [DOI: 10.1016/j.cell.2007.01.029]
[51] Chiva-Blanch G, Peña E, Cubedo J, García-Arguinzonis M, Pané A, Gil PA, et al. Molecular mapping of platelet hyperreactivity in diabetes: the stress proteins complex HSPA8/Hsp90/CSK2α and platelet aggregation in diabetic and normal platelets. Translational Research. 2021;235:1–14.
[52] Chakraborty S, Martines C, Porro F, Fortunati I, Bonato A, Dimishkovska M, et al. B-cell receptor signaling and genetic lesions in TP53 and CDKN2A/CDKN2B cooperate in Richter transformation. Blood, The Journal of the American Society of Hematology. 2021;138(12):1053–66. [DOI: 10.1182/blood.2020008276]
[53] Deng F-Y, Lei S-F, Zhang Y, Zhang Y-L, Zheng Y-P, Zhang L-S, et al. Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans. Molecular & Cellular Proteomics. 2011;10(11). [DOI: 10.1074/mcp.M111.011700]
[54] Whitby MC. The FANCM family of DNA helicases/translocases. DNA repair. 2010;9(3):224–36. [DOI: 10.1016/j.dnarep.2009.12.012]
[55] Bogdanova N, Horst J, Chlystun M, Croucher PJ, Nebel A, Bohring A, et al. A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss. Human molecular genetics. 2007;16(5):573–8. [DOI: 10.1093/hmg/ddm017]
[56] Munson P, Lam YW, Dragon J, MacPherson M, Shukla A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells. Faseb j. 2018;32(8):4328–42. [DOI: 10.1096/fj.201701291RR]
[57] Huang CK, Sun Y, Lv L, Ping Y. ENO1 and Cancer. Molecular Therapy-Oncolytics. 2022;24:288–98. [DOI: 10.1016/j.omto.2021.12.026]
[58] Erdei A, Fust G, Gergely J. The role of C3 in the immune response. Immunology today. 1991;12(9):332–7. [DOI: 10.1016/0167-5699(91)90011-H]
[59] Dayton TL, Jacks T, Vander Heiden MG. PKM 2, cancer metabolism, and the road ahead. EMBO reports. 2016;17(12):1721–30. [DOI: 10.15252/embr.201643300]
[60] Mihaylova V, Müller JS, Vilchez JJ, Salih MA, Kabiraj MM, D’Amico A, et al. Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes. Brain. 2008;131(3):747–59. [DOI: 10.1093/brain/awm325]
[61] Urbańska K, Orzechowski A. Unappreciated role of LDHA and LDHB to control apoptosis and autophagy in tumor cells. International journal of molecular sciences. 2019;20(9):2085. [DOI: 10.3390/ijms20092085]
[62] Shi Y, Ruiz N, Taib R, Choi E, Chen F, editors. Galvanic skin response (GSR) as an index of cognitive load. CHI'07 extended abstracts on Human factors in computing systems; 2007.
[63] Corona A, Blobe GC. The role of the extracellular matrix protein TGFBI in cancer. Cellular signalling. 2021;84:110028. [DOI: 10.1016/j.cellsig.2021.110028]
[64] Kuner R, Fälth M, Pressinotti NC, Brase JC, Puig SB, Metzger J, et al. The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer. Journal of molecular medicine. 2013;91(2):237–48. [DOI: 10.1007/s00109-012-0949-1]
[65] Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, et al. A census of human cancer genes. Nature reviews cancer. 2004;4(3):177–83. [DOI: 10.1038/nrc1299]
[66] Zhu Z, Zhang W, Huo S, Huang T, Cao X, Zhang Y. TUBB, a robust biomarker with satisfying abilities in diagnosis, prognosis, and immune regulation via a comprehensive pan-cancer analysis. Frontiers in Molecular Biosciences. 2024;11:1365655. [DOI: 10.3389/fmolb.2024.1365655]
[67] Lei Y, Yu T, Li C, Li J, Liang Y, Wang X, et al. Expression of CAMK1 and its association with clinicopathologic characteristics in pancreatic cancer. Journal of Cellular and Molecular Medicine. 2021;25(2):1198–206. [DOI: 10.1111/jcmm.16188]
[68] Pihl R, Jensen RK, Poulsen EC, Jensen L, Hansen AG, Thøgersen IB, et al. ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism. Science advances. 2021;7(2):eaba7381. [DOI: 10.1126/sciadv.aba7381]
[69] Lu W, Cui J, Wang W, Hu Q, Xue Y, Liu X, et al. PPIA dictates NRF2 stability to promote lung cancer progression. Nature Communications. 2024;15(1):4703. [DOI: 10.1038/s41467-024-48364-4]
[70] Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature genetics. 2007;39(8):1013–7. [DOI: 10.1038/ng2078]
[71] Zhang X, Yang W, Chen K, Zheng T, Guo Z, Peng Y, et al. The potential prognostic values of the ADAMTS-like protein family: an integrative pan-cancer analysis. Annals of Translational Medicine. 2021;9(20):1562. [DOI: 10.21037/atm-21-4946]
[72] Raturi A, Gutiérrez T, Ortiz-Sandoval C, Ruangkittisakul A, Herrera-Cruz MS, Rockley JP, et al. TMX1 determines cancer cell metabolism as a thiol-based modulator of ER–mitochondria Ca2+ flux. Journal of Cell Biology. 2016;214(4):433–44. [DOI: 10.1083/jcb.201512077]
- Abstract Viewed: 43 times
- PDF Downloaded: 28 times