Dataset Information

In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma.

ABSTRACT:

Background

ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC.

Methods

Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms.

Result

The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC.

Conclusion

ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

SUBMITTER: Zhu Z

PROVIDER: S-EPMC7871357 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma.

Zhu Zhipeng Z Xu Jiuhua J Wu Xiaofang X Lin Sihao S Li Lulu L Ye Weipeng W Huang Zhengjie Z

Technology in cancer research & treatment 20210101

<h4>Background</h4><i>ADAMTS5</i> has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of <i>ADAMTS5</i> in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC.<h4>Methods</h4>Firstly, the association of <i>ADAMTS5</i> expression and clinicopathological parameters was evaluated by in GSE14520. Next, ...[more]

PMID: 33522433

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Project description:BackgroundThe regulator of calcineurin 1 (RCAN1) is expressed in multiple organs, including the heart, liver, brain, and kidney, and is closely linked to the pathogenesis of cardiovascular diseases, Down syndrome, and Alzheimer's disease. It is also implicated in the development of various organ tumors; however, its potential role in hepatocellular carcinoma (HCC) remains poorly understood. Therefore, the objective of this study was to investigate the potential mechanisms of RCAN1 in HCC through bioinformatics analysis.MethodsWe conducted a joint analysis based on the NCBI and TCGA databases, integrating both bulk transcriptome and single-cell analyses to examine the principal biological functions of RCAN1 in HCC, as well as its roles related to phenotype, metabolism, and cell communication. Subsequently, an RCAN1-overexpressing cell line was established, and the effects of RCAN1 on tumor cells were validated through in vitro experiments. Moreover, we endeavored to identify potential related drugs using molecular docking and molecular dynamics simulations.ResultsThe expression of RCAN1 was found to be downregulated in 19 types of cancer tissues and upregulated in 11 types of cancer tissues. Higher levels of RCAN1 expression were associated with improved patient survival. RCAN1 was predominantly expressed in hepatocytes, macrophages, endothelial cells, and monocytes, and its high expression not only closely correlated with the distribution of cells related to the HCC phenotype but also with the distribution of HCC cells themselves. Additionally, Rcan1 may directly or indirectly participate in metabolic pathways such as alanine, aspartate, and glutamate metabolism, as well as butanoate metabolism, thereby influencing tumor cell proliferation and migration. In vitro experiments confirmed that RCAN1 overexpression promoted apoptosis while inhibiting proliferation and invasion of HCC cells. Through molecular docking of 1615 drugs, we screened brompheniramine as a potential target drug and verified our results by molecular dynamics.ConclusionIn this study, we revealed the relationship between RCAN1 and HCC through bioinformatics methods, verified that RCAN1 can affect the progress of the disease through experiments, and finally identified potential therapeutic drugs through drug molecular docking and molecular dynamics.

Dataset Information

In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma.

Background

Methods

Result

Conclusion

Publications

In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma.

Similar Datasets

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