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Comprehensive transcriptomic analysis of papillary thyroid cancer: potential biomarkers associated with tumor progression

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Abstract

Purpose

Identification of stage-specific prognostic/predictive biomarkers in papillary thyroid carcinoma (PTC) could lead to its more efficient clinical management. The main objective of this study was to characterize the stage-specific deregulation in genes and miRNA expression in PTC to identify potential prognostic biomarkers.

Methods

495 RNASeq and 499 miRNASeq PTC samples (stage I–IV) as well as, respectively, 56 and 57 normal samples were retrieved from The Cancer Genome Atlas (TCGA). Differential expression analysis was performed using DESeq 2 to identify deregulation of genes and miRNAs between sequential stages. To identify the minority of patients who progress to higher stages, we performed clustering analysis on stage I RNASeq data. An independent PTC RNASeq data set (BioProject accession PRJEB11591) was also used for the validation of the results.

Results

LTF and PLA2R1 were identified as two promising biomarkers down-regulated in a subgroup of stage I (both in TCGA and in the validation data set) and in the majority of stage IV of PTC (in TCGA data set). hsa-miR-205, hsa-miR-509-2, hsa-miR-514-1 and hsa-miR-514-2 were also detected as up-regulated miRNAs in both PTC patients with stage I and stage III. Hierarchical clustering of stage I samples showed substantial heterogeneity in the expression pattern of PTC indicating the necessity of categorizing stage I patients based on the expressional alterations of specific biomarkers.

Conclusion

Stage I PTC patients showed large amount of expressional heterogeneity. Therefore, risk stratification based on the expressional alterations of candidate biomarkers could be an important step toward personalized management of these patients.

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Availability of data and material

Data are available at (http://portal.gdc.cancer.gov/).

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Acknowledgements

The authors gratefully acknowledge the supports provided by Iran University of Medical Sciences (Grant number 33444).

Funding

Financial support was provided by Iran University of Medical Sciences (Grant number 33444).

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Authors and Affiliations

  1. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran

    N. Hosseinkhan, M. Honardoost & M. E. Khamseh

  2. Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland

    K. Blighe & C. B. T. Moore

Authors
  1. N. Hosseinkhan
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  2. M. Honardoost
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  3. K. Blighe
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  4. C. B. T. Moore
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  5. M. E. Khamseh
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Contributions

M. K designed and supervised the project. N. H performed the data analyses and wrote the manuscript. K. B, M. K and M. H commented on the manuscript. T. M reviewed the paper.

Corresponding author

Correspondence to M. E. Khamseh.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

Ethical approval for this study was obtained from The Committee for Ethics in Research Involving Human Subjects, Iran University of Medical Sciences (Ethical code—IR.IUMS.REC.1397.203).

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List of up and down-regulated genes in different clusters of stage I (XLS 36 kb)

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Hosseinkhan, N., Honardoost, M., Blighe, K. et al. Comprehensive transcriptomic analysis of papillary thyroid cancer: potential biomarkers associated with tumor progression. J Endocrinol Invest 43, 911–923 (2020). https://doi.org/10.1007/s40618-019-01175-7

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  • DOI: https://doi.org/10.1007/s40618-019-01175-7

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