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Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications

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Abstract

Background

Gastric cancer (GC) is the fifth most common cancer worldwide and the most commonly diagnosed cancer in Iran. The nervous system provides proximity to tumor cells by releasing neurotransmitters such as dopamine and presenting them to the corresponding receptor-bearing tumors. While nerve fibers infiltrate the tumor microenvironment, little is known about the expression levels of dopamine (DA), dopamine receptors (DRs), and catechol-O-methyltransferase (COMT) in GC patients.

Methods

DRs and COMT expression were analyzed in 45 peripheral blood mononuclear cells (PBMCs) and 20 paired tumor and adjacent tissue of GC patients by quantitative polymerase chain reaction. DA was measured in plasma specimens using enzyme-linked immunosorbent assay. Protein-protein interaction analysis was carried out to identify GC-related hub genes.

Results

Increased expression of DRD1-DRD3 was found in tumor specimens compared with adjacent non-cancerous specimens (P < 0.05). A positive correlation was found between DRD1 and DRD3 expression (P = 0.009); DRD2 and DRD3 expression (P = 0.04). Plasma levels of dopamine were significantly lower in patients (1298 pg/ml) than in controls (4651 pg/ml). DRD1–DRD4 and COMT were up-regulated in PBMCs of patients compared with controls (P < 0.0001). Bioinformatic analyses showed 30 hub genes associated with Protein kinase A and extracellular signal-regulated kinase signaling pathways.

Conclusions

The findings indicated dysregulation of DRs and COMT mRNA expression in GC and suggest that the brain- gastrointestinal axis may mediate gastric cancer development. Network analysis revealed that combination treatments could be considered for optimizing and improving the precision treatment of GC.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

Our Sincere thanks to all participants for donating samples and Mazandaran University of Medical Sciences and National Institute of Genetic Engineering and Biotechnology for financial support and also Professor Lira Sergio A from Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, the USA for scientific support and critical reading of the manuscript.

Funding

The current research was supported by Mazandaran University of Medical Sciences (Grant No. MAZUMS.7870) and the National Institute of Genetic Engineering and Biotechnology (Grant No.772).

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Authors and Affiliations

  1. Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, P.O. Box: 1497716316, Iran

    Omolbanin Amjadi & Ghasem Ahangari

  2. Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Akbar Hedayatizadeh-Omran & Ehsan Zaboli

  3. Department of Surgery, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mohammad Mehdi Ghaffari-Hamedani

  4. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ghasem Janbabaei

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Contributions

Conception and design: GA. Data acquisition: EZ. Writing manuscript and performing experiments: OA. Analysis and interpretation of data: OA and EZ. Providing primary tumor and adjacent samples: MMG. Review and/or revision of the manuscript: GJ and AH. Study supervision: GA. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ghasem Ahangari.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Ethics Committee of Mazandaran University of Medical Sciences (IR.MAZUMS.REC.1400.7870).

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Informed consent was obtained from all individual participants included in the study.

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Patients voluntarily signed informed consent regarding publishing their data.

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Amjadi, O., Hedayatizadeh-Omran, A., Zaboli, E. et al. Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications. Mol Biol Rep 50, 6529–6542 (2023). https://doi.org/10.1007/s11033-023-08541-y

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  • DOI: https://doi.org/10.1007/s11033-023-08541-y

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