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The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma

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Abstract

Background

Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC.

Materials and methods

In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2.

Results

The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801).

Conclusion

Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

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Funding

This work was supported by National Science Fund, Bulgaria under Grant KP-06-H23/4 and Medical University – Sofia, project ‘’Young Researcher’’, contract 126/04.06.2021.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, Medical Faculty, Medical University, Sofia, Bulgaria

    Anastasia Ormandjieva & Milena Ivanova

  2. Clinic of Clinical Immunology with Stem Cell Bank, University Hospital ’’Alexandrovska’’, Sofia, Bulgaria

    Milena Ivanova

  3. University Hospital “St. Anna”, Sofia, Bulgaria

    Stanislav Yordanov

  4. Department of Dental, Oral and Maxillofacial surgery, FDM, Medical University - Sofia, Sofia, Bulgaria

    Hristo Stoyanov & Elitsa Deliverska

  5. Department of Experimental Research, Medical University Pleven, Pleven, Bulgaria

    Velizar Shivarov

Authors
  1. Anastasia Ormandjieva
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  2. Stanislav Yordanov
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  4. Elitsa Deliverska
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  5. Velizar Shivarov
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  6. Milena Ivanova
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Contributions

Anastasia Ormandjieva: Data curation; Analysis and methodology; Software; Validation; Visualization; Writing-original draft. Stanislav Yordanov: Investigation; Resources. Hristo Stoyanov: Resources. Elitsa Deliverska: Investigation; Resources; Supervision. Velizar Shivarov: Conceptualization, data analysis, propose research. Milena Ivanova: Conceptualization; Data curation; Funding acquisition; Investigation; Project administration; Supervision; Resources.

Corresponding author

Correspondence to Anastasia Ormandjieva.

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Ethics approval statement

The principles of the Declaration of Helsinki were strictly followed during the study. Ethical approval was granted for this study by Research Ethics Committee at Medical University - Sofia with the approval number №15/19.05.2021.

Patient consent statement

All patients and healthy controls provided informed consent for genetic testing as part of the institutional review board’s approved standard-operating procedures at our institutions.

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Ormandjieva, A., Yordanov, S., Stoyanov, H. et al. The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma. Mol Biol Rep 50, 7245–7252 (2023). https://doi.org/10.1007/s11033-023-08629-5

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  • DOI: https://doi.org/10.1007/s11033-023-08629-5

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