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In search of new stratification strategies: tissue proteomic profiling of papillary thyroid microcarcinoma in patients with localized disease and lateral neck metastases

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Abstract

Introduction

Papillary thyroid carcinomas (PTC) are the most common thyroid malignancies that are often diagnosed as microcarcinomas when the tumor is less than one centimetre in diameter. Currently, there are no valid stratification strategies that would reliably assess the risk of lateral neck metastases and optimize surgical treatment.

Materials and methods

Aiming to find potential tissue biomarkers of metastatic potential, we conducted a cross-sectional proteomic pilot study on formalin-fixed paraffin-embedded tissues of metastatic (N = 10) and non-metastatic (N = 10) papillary thyroid microcarcinoma patients. Samples were analysed individually using liquid chromatography/mass spectrometry, and the differentially expressed proteins (DEP) were functionally annotated.

Results

We identified five overexpressed DEPs in the metastatic group (EPB41L2, CSE1L, GLIPR2, FGA and FGG) with a known association to tumour biology. Using bioinformatic-based tools, we found markedly different profiles of significantly enriched biological processes between the two groups.

Conclusions

The identified DEPs might have a role as potential tissue biomarkers for PTC metastases. However, further prospective research is needed to confirm our findings.

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Data availability

The data that support the findings of this study are available on request from the Journal of Cancer Research and Clinical Oncology.

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Acknowledgements

The authors would like to thank the study participants. he study was supported by the BIMIS—Biomedical Research Center Šalata, University of Zagreb School of Medicine, 10000 Zagreb, Croatia and infrastructural project CIuK (European Regional Development Fund, grant number KK.01.1.1.02.0016).

Funding

Scientific Center of Excellence for Reproductive and Regenerative Medicine (project “Reproductive and regenerative medicine—exploration of new platforms and potentials”, Grant Agreement KK.01.1.1.01.0008, which is funded by the European Union through the European Regional Development Fund).

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Authors and Affiliations

  1. Department of Otorhinolaryngology and Head and Neck Surgery, Sestre Milosrdnice University Hospital Center, 10000, Zagreb, Croatia

    Filip Matovinovic, Andro Košec & Vladimir Bedekovic

  2. Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000, Zagreb, Croatia

    Rudjer Novak & Lovorka Grgurevic

  3. Department of Clinical Immunology, Allergology and Rheumatology, University Hospital Dubrava, 10000, Zagreb, Croatia

    Stela Hrkac

  4. Department of Pulmonology, University Hospital Dubrava, 10000, Zagreb, Croatia

    Grgur Salai

  5. Department of Chemistry, Faculty of Science, University of Zagreb, 10000, Zagreb, Croatia

    Marko Mocibob & Marija Pranjic

  6. Department of Anatomy, “Drago Perovic”, School of Medicine, University of Zagreb, 10000, Zagreb, Croatia

    Lovorka Grgurevic

  7. School of Medicine, University of Zagreb, 10000, Zagreb, Croatia

    Andro Košec

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  1. Filip Matovinovic
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Contributions

Conceptualization—LG, RN and FM; investigation, methodology—FM, RN and MP; formal analysis, visualization—FM, RN and MP; supervision, validation—LG and MM; writing—original draft—LG, RN, FM, GS, SH and MP; writing—review and editing—all authors. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Lovorka Grgurevic.

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432_2023_5452_MOESM1_ESM.jpg

Supplementary Figure 1. Violin plot showing the analysed experimental samples. Proteins were identified by MaxQuant 2.3.1.0. software and quantified by using the label free quantification (LFQ) algorithm. Log 2 of LFQ are plotted on the y axis to show sample consistency. (JPG 322 KB)

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Matovinovic, F., Novak, R., Hrkac, S. et al. In search of new stratification strategies: tissue proteomic profiling of papillary thyroid microcarcinoma in patients with localized disease and lateral neck metastases. J Cancer Res Clin Oncol 149, 17405–17417 (2023). https://doi.org/10.1007/s00432-023-05452-0

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