Identification of four methylation-driven genes as candidate biomarkers for monitoring single-walled carbon nanotube-induced malignant transformation of the lung

Xie, Dongli; Luo, Xiaogang

doi:10.1016/j.taap.2020.115391

Cited by 12 publications

(12 citation statements)

References 62 publications

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“…Furthermore, FN1 and THBS2 were also upregulated genes in asbestos-induced malignant transformation of MeT5A cells or mice ( Table S1 ); in our previous study on CNT-induced malignant transformation of lung cells, FN1 was likewise highly expressed. 26 These findings suggest UGCG and/or CHPF2 combination with FN1 and THBS2 may be more specific for the diagnosis of CNT-induced MPM. This conclusion could be demonstrated according to the sensitivity results in GSE2549 analysis (FN1+THBS2, 60%; FN1+UGCG+THBS2, 95%; FN1+UGCG+CHPF2+THBS2, 80%) and specificity results in GSE51042 analysis (FN1+THBS2, 85.37%; FN1+UGCG+THBS2, 97.56%; FN1+UGCG+CHPF2+THBS2, 97.56%) ( Table 4 ).…”

Section: Resultsmentioning

confidence: 81%

“…However, current studies on the molecular mechanisms of CNT-induced MPM remain rare 12 , 13 , 17 and no studies linked CNT-exposed in vitro and in vivo models with MPM patient samples as reports for lung cancer. 26 , 35 In the present study, we, for the first time, attempted to screen concordant genes differentially expressed both in CNT-exposed MeT5A cells and mice compared with controls and validate the expression, diagnostic and prognostic abilities of hub genes in specimens from MPM patients. Based on WGCNA and PPI network analyses, 20 genes were considered as hub module genes associated with the development of CNT-induced MPM.…”

Section: Discussionmentioning

confidence: 99%

“…However, current studies on the molecular mechanisms of CNT-induced MPM remain rare 12,13,17 and no studies linked CNT-exposed in vitro and in vivo models with MPM patient samples as reports for lung cancer. 26,35 In the present study, we, for the first time, attempted to screen concordant genes differentially expressed both in CNT-exposed MeT5A cells and mice compared with controls and validate the expression, diagnostic and prognostic Based on WGCNA and PPI network analyses, 20 genes were considered as hub module genes associated with the development of CNT-induced MPM. Four of them (FN1, UGCG, CHPF2 and THBS2) were found to be significantly associated with OS; significantly upregulated in MPM specimens compared to control tissues; and they could effectively predict the MPM risk with an overall accuracy >0.9 using the gene-combination.…”

Section: Discussionmentioning

confidence: 99%

“…The WGCNA package in R (v1.61; https://cran.r-project.org/web/packages/WGCNA/index.html ) 18 was used to construct the co-expression network based on the expression data of all mRNAs in the GSE48855 dataset. As described previously, 26 the first step was to determine the soft-thresholding power (β) using the pickSoftThreshold function of WGCNA according to the scale-free topology criterion. Then, the adjacency matrix was converted into a topological overlap matrix (TOM) to construct a dendrogram.…”

Section: Methodsmentioning

confidence: 99%

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Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Xie

et al. 2021

IJGM

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Background Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM. Methods Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers. Results WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1). Conclusion These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.

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Section: Resultsmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

“…However, current studies on the molecular mechanisms of CNT-induced MPM remain rare 12,13,17 and no studies linked CNT-exposed in vitro and in vivo models with MPM patient samples as reports for lung cancer. 26,35 In the present study, we, for the first time, attempted to screen concordant genes differentially expressed both in CNT-exposed MeT5A cells and mice compared with controls and validate the expression, diagnostic and prognostic Based on WGCNA and PPI network analyses, 20 genes were considered as hub module genes associated with the development of CNT-induced MPM. Four of them (FN1, UGCG, CHPF2 and THBS2) were found to be significantly associated with OS; significantly upregulated in MPM specimens compared to control tissues; and they could effectively predict the MPM risk with an overall accuracy >0.9 using the gene-combination.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Xie

et al. 2021

IJGM

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“…38 Multi-walled CNTs embedded in pleural membrane activated macrophages that secreted IL-1-beta, which amplify inflammation in mesothelial cells. 39 Crystal structure and route of exposure Different crystalline structures of nanoparticles can exhibit toxicity differently. Nanoparticles can show different oxidative mechanisms, cellular uptake and subcellular localization based upon their crystalline structure.…”

Section: Particle Size and Shapementioning

confidence: 99%

Inorganic Nanoparticles: Toxic Effects, Mechanisms of Cytotoxicity and Phytochemical Interactions

et al. 2021

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During the last few decades, nanotechnology has gained many applications in almost all fields of life because of the unique properties of nanoparticles. Nanotechnology has specially marked its name in the field of medicine. However, nanoparticles toxicity is detrimental to human health and is a prime concern in applied medicine. They can cause insomnia, vertigo, madarosis, epistaxis, hypokalemia, lymphopenia, Alzheimer's and Parkinson's diseases, etc. There is a gap in knowledge regarding the study of the toxicological effects of nanoparticles. Mechanisms that are responsible for this toxicity are not fully understood yet. Phytochemicals have natural therapeutic effects of reducing metal nanoparticles' toxicity by acting as stabilizers and nontoxic reducing agents. However, the interaction between phytochemicals and nanoparticles is remained to be elucidated. This review will provide in-depth knowledge about the various types of inorganic nanoparticles and their associated toxicities, key parameters determining the toxic behaviour of nanoparticles, and the mechanisms behind their cytotoxicity. It also emphasizes the need for further research to understand the interaction between various phytochemicals and nanoparticles for therapeutic purposes.

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The critical role of epigenetic mechanisms involved in nanotoxicology

Sun

et al. 2022

WIREs Nanomed Nanobiotechnol

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Over the past decades, nanomaterials (NMs) have been widely applied in the cosmetic, food, engineering, and medical fields. Along with the prevalence of NMs, the toxicological characteristics exhibited by these materials on health and the environment have gradually attracted attentions. A growing number of evidences have indicated that epigenetics holds an essential role in the onset and development of various diseases. NMs could cause epigenetic alterations such as DNA methylation, noncoding RNA (ncRNA) expression, and histone modifications. NMs might alternate either global DNA methylation or the methylation of specific genes to affect the biological function. Abnormal upregulation or downregulation of ncRNAs might also be a potential mechanism for the toxic effects caused by NMs. In parallel, the phosphorylation, acetylation, and methylation of histones also take an important part in the process of NMs‐induced toxicity. As the adverse effects of NMs continue to be explored, mechanisms such as chromosomal remodeling, genomic imprinting, and m6A modification are also gradually coming into the limelight. Since the epigenetic alterations often occur in the early development of diseases, thus the relevant studies not only provide insight into the pathogenesis of diseases, but also screen for the prospective biomarkers for early diagnosis and prevention. This review summarizes the epigenetic alterations elicited by NMs, hoping to provide a clue for nanotoxicity studies and security evaluation of NMs. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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Identification of four methylation-driven genes as candidate biomarkers for monitoring single-walled carbon nanotube-induced malignant transformation of the lung

Cited by 12 publications

References 62 publications

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Inorganic Nanoparticles: Toxic Effects, Mechanisms of Cytotoxicity and Phytochemical Interactions

The critical role of epigenetic mechanisms involved in nanotoxicology

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