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Identification and validation of cuproptosis-related genes for diagnosis and therapy in nonalcoholic fatty liver disease

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Abstract

In recent years, nonalcoholic fatty liver disease (NAFLD) has become a more serious public health issue worldwide. This study strived to investigate the molecular mechanism of pathogenesis of NAFLD and explore promising diagnostic and therapeutic targets for NAFLD. Raw data from GSE130970 were downloaded from the Gene Expression Omnibus database. We used the dataset to analyze the expression levels of cuproptosis-related genes in NAFLD patients and healthy controls to identify the differentially expressed cuproptosis-related genes (DECRGs). The relationship and potential mechanism between DECRGs and clinicopathological factors were examined by enrichment analysis and two consensus clustering methods. We screened key DECRGs based on Random Forest (RF), and then verified the key DECRGs in NAFLD patients, high-fat diet (HFD)–fed mice, and palmitic acid–induced AML12 cells. ROC analysis showed good diagnostic function of DECRGs in normal and NAFLD liver tissue. Two consensus clusters indicated the important role of cuproptosis in the development of NAFLD. We screened for key DECRGs (DLD, DLAT) based on RF and found a close relationship between the DECRGs and clinicopathological factors. We collected clinical blood samples to verify the differences in gene expression levels by qPCR. In addition, we further verified the expression levels of DLD and DLAT in HFD mice and AML12 cells, which showed the same results. This study provides a novel perspective on the pathogenesis of NAFLD. We identified two cuproptosis-related genes that are closely related to NAFLD. These genes may play a significant role in the molecular pathogenesis of NAFLD, which may be useful to make progress in the diagnosis and treatment of NAFLD.

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Data availability

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: GSE130970; further inquiries can be directed to the corresponding author.

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Acknowledgements

The authors all would like to thank the GEO database and the authors who provided their platforms and contributors for uploading their meaningful datasets. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This work was supported by the Shandong Provincial Natural Science Foundation (Grant No. ZR2022MH182 and Grant No. ZR2021QH119), and the National Natural Science Foundation of China (Grant No. 82300892).

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Authors and Affiliations

  1. Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Jinquan Li, Xiaohan Ma, Ruiqi Liu, Cuicui Xu, Qin He & Ming Dong

  2. Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, China

    Qin He & Ming Dong

  3. Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong, China

    Qin He & Ming Dong

  4. Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, China

    Qin He & Ming Dong

  5. Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Yi Zhang

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Contributions

JL carried out experiments and wrote the manuscript, YZ, XM, RL, CX downloaded, arranged, analyzed, and validated the data. MD, QH designed the experiment and reviewed and approved the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qin He or Ming Dong.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Gene Expression Omnibus (GEO) database belongs to public databases. Patients / participants provided written informed consent to participate in this study. Individual written informed consent has been obtained for publishing any potentially identifiable images or data contained in this article, our study is based on open-source data with no ethical issues and other conflicts of interest. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Qilu Hospital of Shandong University.(KYLL-202210–070-1). All animal experimental protocols were approved by the Animal Ethics Committee of Qilu Hospital of Shandong University.(DWLL-2022–090).

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Li, J., Zhang, Y., Ma, X. et al. Identification and validation of cuproptosis-related genes for diagnosis and therapy in nonalcoholic fatty liver disease. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04957-7

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