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The association between several autophagy-related genes and their prognostic values in hepatocellular carcinoma: a study on the foundation of TCGA, GEPIA and HPA databases

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Abstract

Background

The purpose of this study was to investigate the relationship between the expression of autophagy-related genes and prognosis in hepatocellular carcinoma (HCC).

Methods and Results

We selected three autophagy-related genes (ATG3, ATG7, and ATG9A) from gene expression data of liver cancer patients in The Cancer Genome Atlas (TCGA) database by Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis, and Gene Set Enrichment Analysis (GSEA). Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were applied to testify the credibility of our results. The expression levels of ATG3, ATG7, and ATG9A were verified by real-time quantitative PCR (RT-qPCR) in normal liver cells (L02) and three HCC cell lines (HepG2, Hep3b, and Li-7). Data analysis results from TCGA showed high ATG3, ATG7, ATG9A expression in HCC tumor tissues. Kaplan-Meier survival analysis showed that the survival rate of the high expression group of ATG3, ATG7, and ATG9A was all significantly lower than the low expression group. GSEA analysis showed that many signaling pathways (such as the regulation of autophagy, glycine serine and threonine metabolism, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, mammalian target of rapamycin (mTOR) signaling pathway, as well as P53 signaling pathway) were differentially enriched in HCCs with ATG3, ATG7, and ATG9A expression. GEPIA and RT-qPCR also identified that the mRNA expression level of ATG3, ATG7, and ATG9A in normal liver cells were significantly lower than in HCC cells. High protein expression of ATG3, ATG7, and ATG9A was displayed in HCCs from the HPA database.

Conclusions

The ATG3, ATG7, ATG9A might be utilized as prognostic biomarkers for liver cancer.

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Acknowledgements

This work was supported by the WU JIEPING MEDICAL FOUNDATION of China (Grant NO. 320.6750.19089-103 and Grant NO. 320.6750.19089-75), and Beijing High-level Public Health Technical Personnel Construction Project (Grant NO. 2022-2-014).

Funding

This study was funded by the WU JIEPING MEDICAL FOUNDATION of China (Grant NO. 320.6750.19089-103 and Grant NO. 320.6750.19089-75), Beijing High-level Public Health Technical Personnel Construction Project (Grant NO. 2022-2-014).

Author information

Authors and Affiliations

  1. College of Biological Sciences and Biotechnology, Beijing Forestry University, 100083, Beijing, China

    Xueying Zhao & Zhengrong Yuan

  2. Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, 100015, Beijing, China

    Shangqi Yin, Jingren Shi, Mei Zheng, Chaonan He, Huan Meng, Ying Han, Jin Chen, Jinyu Han & Yajie Wang

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  1. Xueying Zhao
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Contributions

Formal analysis, Data Curation, Writing - Original Draft, Validation, Visualization, and Writing - Review & Editing were performed by Xueying Zhao. Investigation, Supervision, Data Analysis, Writing - Review & Editing were performed by Shangqi Yin. Project administration, Resources, and Data Analysis were performed by Jingren Shi, Mei Zheng, Chaonan He, Huan Meng, Ying Han, Jin Chen, and Jinyu Han. Conceptualization, Supervision, Writing - Review & Editing, Data Analysis were performed by Zhengrong Yuan and Yajie Wang. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Zhengrong Yuan or Yajie Wang.

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Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Patients do not need to give informed consent to this study because the analysis used anonymous clinical data from the TCGA database and retained the confidentiality of patients.

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The authors agree to the publication of the article and tacitly or explicitly by the responsible authorities where the work was carried out. If the article is accepted, it will not be published elsewhere in the same form, in English or any other language (including electronic versions) without the written consent of the copyright holder.

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The authors Xueying Zhao and Shangqi Yin contributed equally to this work.

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Zhao, X., Yin, S., Shi, J. et al. The association between several autophagy-related genes and their prognostic values in hepatocellular carcinoma: a study on the foundation of TCGA, GEPIA and HPA databases. Mol Biol Rep 49, 10269–10277 (2022). https://doi.org/10.1007/s11033-022-07426-w

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