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Bioinformatics Identification of Therapeutic Gene Targets for Gastric Cancer

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Abstract

Introduction

The global prevalence of gastric cancer (GC) is increasing, and novel chemotherapeutic targets are needed.

Methods

We searched for potential biomarkers for GC in three microarray data sets within the Gene Expression Omnibus (GEO) database. FunRich (v3.1.3) was used to perform Gene Ontology (GO) analyses and STRUN and Cytoscape (v3.6.0) were employed to construct a protein–protein interaction (PPI) network. To explore hub gene expression and survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier (KM) plotter. Drugs that were closely related to key genes were screened by the Gene Set Cancer Analysis (GSCA), and relevant correlations were verified experimentally. We validated that the sensitivity of a GC cell line to these drugs was correlated with fibrillin 1 (FBN1) mRNA expression levels.

Results

We identified 83 upregulated and 133 downregulated differentially expressed genes (DEGs) and these were enriched with regards to their cellular component (extracellular and exosomes), molecular function (extracellular matrix structural constituent and catalytic activity), and biological process (cell growth and/or maintenance and metabolism). The biological pathways most prominently involved were epithelial-to-mesenchymal transition (EMT) and β3 integrin cell surface interactions. For the PPI network, we selected 10 hub genes, and 70% of these were significantly connected to poor overall survival (OS) in patients with GC. We found a significant link between the expression of FBN1 and two small molecule drugs (PAC-1 and PHA-793887).

Conclusions

Overall, we suggest that these hub genes can be used as biomarkers and novel targets for GC. FBN1 may be associated with drug resistance in gastric cancer.

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Acknowledgements

The authors thank Fu Liu, Shengqian Li and Ming Yang for providing valuable technical supports.

Funding

This work was supported by National Natural Science Foundation of China (81903660); Sichuan Science and Technology Plan Project (2019YJ0386); Nanchong City and School Cooperation Project (19SXHZ0201, 20SXQT0101); Affiliated Hospital of North Sichuan Medical College Plan Projects (2021YS009, 2022JB006). The journal’s Rapid Service fees were funded by Affiliated Hospital of North Sichuan Medical College.

Medical Writing and Editorial Assistance

Editorial assistance in the preparation of this article was provided by Dr. Qiang Ma of North Sichuan Medical College.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

All authors contributed to the study conception and design. Acquisition of data was performed by Yuanting Li, Minghao Chen and Qing Chen. Material preparation was performed by Yuanting Li and Minghao Chen. Bioinformatics analysis and experiments were performed by Yuanting Li, Minghao Chen and Min Yuan. Data analysis was performed by Yuanting Li, Xi Zeng, Yan Zeng and Meibo He. The first draft of the manuscript was written by Baiqiang Wang and Bin Han. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Disclosures

All named authors confirm that they have no conflicts of interest to declare.

Compliance with Ethics Guidelines

This article does not contain any studies with human participants or animals performed by any of the authors.

Data Availability

All data is available under reasonable request.

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Author notes

  1. Yuanting Li and Minghao Chen contributed equally to this work.

Authors and Affiliations

  1. GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Yuanting Li, Qing Chen, Min Yuan, Xi Zeng, Yan Zeng, Meibo He & Bin Han

  2. Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Yan Zeng, Meibo He, Baiqiang Wang & Bin Han

  3. Institute of Pharmacy, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Yuanting Li, Qing Chen, Min Yuan, Xi Zeng, Meibo He & Bin Han

  4. Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Minghao Chen

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  1. Yuanting Li
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Correspondence to Baiqiang Wang or Bin Han.

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Li, Y., Chen, M., Chen, Q. et al. Bioinformatics Identification of Therapeutic Gene Targets for Gastric Cancer. Adv Ther 40, 1456–1473 (2023). https://doi.org/10.1007/s12325-023-02428-x

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