Marianna Papadaki¹, Christina Piperi², Georgia Damoraki³ and Evangelia Papadavid¹*

¹2^nd Department of Dermatology and Venereal Diseases, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
²Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
³4^th Department of Internal Medicine, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

*Corresponding Author: Evangelia Papadavid, 2^nd Department of Dermatology and Venereal Diseases, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Received: January 21, 2022; Published: March 14, 2022

Abstract

Background: The diagnosis of early-stage Mycosis Fungoides (MF) can be very challenging due to overlapping clinicopathologic findings with reactive and inflammatory dermatoses. The aim of this study was to investigate whether selective peripheral blood microRNAs, are involved in CTCL pathogenesis and can be used as potential diagnostic biomarkers to differentiate inflammatory diseases from early MF.

Methods: The expression of miR-148a, miR-338-3p, miR-26a, miR-146a and miR-451 was evaluated in the serum of early MF patients (Ν = 15) using RT-PCR and also measured in skin biopsies (Ν = 10) and CTCL cell lines (My-La and Seax).

Results: Our data showed that miR-26a and miR-146a were significantly upregulated (P < 0.001) in early MF patients compared to controls and could be utilized to differentiate inflammatory skin diseases from early-stage MF. Of importance, miR-451 which has a tumor suppressor role in other hematologic malignancies, was overexpressed in MF.

Conclusions: Altogether these data indicate that liquid biopsy may detect upregulation of specific microRNAs (miR-26a and miR-146a) in early-stage MF and present a reliable non-invasive diagnostic technique. The correlation of liquid biopsy with histological data from the skin biopsy indicates that it may be further used as a supplementary tool to the established criteria for the differential diagnosis of early MF stages from inflammatory skin diseases.

Keywords: CTCL; Diagnosis; miRNA; MF; Biomarkers

References

1. Bagherani N and Smoller BR. “An overview of cutaneous T cell lymphomas”. F1000 Research 5 (2016): 1882.
2. Jawed SI., et al. “Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)”. Journal of the American Academy of Dermatology 70 (2014): 205.e1-205.e16.
3. Massone C., et al. “Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients”. The American Journal of Surgical Pathology 29 (2005): 550-560.
4. Reddy K and Bhawan J. “Histologic mimickers of mycosis fungoides: a review”. Journal of Cutaneous Pathology 34 (2007): 519-525.
5. Michela B. “Liquid Biopsy: A Family of Possible Diagnostic Tools”. Diagnostics8 (2021).
6. DP B. “MicroRNAsGenomics, Biogenesis, Mechanism, and Function”. Cell 116 (2004): 281-297.
7. Navin N., et al. “Tumour evolution inferred by single-cell sequencing”. Nature 472 (2011): 90-95.
8. Gerlinger M., et al. “Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing”. The New England Journal of Medicine 366 (2012): 883-892.
9. Marrugo-Ramírez J., et al. “Blood-based cancer biomarkers in liquid biopsy: A promising non-invasive alternative to tissue biopsy”. International Journal of Molecular Sciences 19 (2018).
10. Wang H., et al. “Circulating microRNAs as potential cancer biomarkers: The advantage and disadvantage”. Clinical Epigenetics 10 (2018).
11. Grasedieck S., et al. “Impact of serum storage conditions on microRNA stability”. Leukemia 26 (2012): 2414-2416.
12. Pan X., et al. “The Potential Role of miR-451 in Cancer Diagnosis, Prognosis, and Therapy”. Molecular Cancer Therapy7 (2013): 1153-1162.
13. Lindahl LM., et al. “Prognostic miRNA classifier in early-stage mycosis fungoides: development and validation in a Danish nationwide study”. Blood 131 (2018): 759-770.
14. Manso R., et al. “Mycosis fungoides progression could be regulated by microRNAs”. PLoS One 13 (2018): e0198477.
15. Dusílková N., et al. “Plasma miR-155, miR-203, and miR-205 are Biomarkers for Monitoring of Primary Cutaneous T-Cell Lymphomas”. International Journal of Molecular Sciences 18 (2017).
16. Sun X., et al. “MiR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression”. Cell Cycle 14 (2015): 243-252.
17. Gao J and Liu QG. “The role of miR-26 in tumors and normal tissues (Review)”. Oncology Letter 2 (2011): 1019-1023.
18. Kim H., et al. “Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship”. Proceedings of the National Academy of Sciences of the United States of America 107 (2010): 2183-2188.
19. da Silva Almeida AC., et al. “The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome”. Nature Genetics 47 (2015): 1465-1470.
20. Kießling MK., et al. “High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade”. Blood 117 (2011): 2433-2440.
21. Cristofoletti C., et al. “Comprehensive analysis of PTEN status in Sezary syndrome”. Blood 122 (2013): 3511-3520.
22. Bandres E., et al. “microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells”. Clinical Cancer Research 15 (2009): 2281-2290.
23. Wang R., et al. “MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14)”. Oncogene 30 (2011): 2644-2658.
24. Redova M., et al. “Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma”. Journal of Translational Medicine 10 (2012): 55.
25. Ju X., et al. “Differential microRNA expression in childhood B- cell precursor acute lymphoblastic leukemia”. Pediatric Hematology and Oncology 26 (2009): 1-10.
26. Godlewski J., et al. “microRNA-451: A conditional switch controlling glioma cell proliferation and migration”. Cell Cycle 9 (2016): 2814-2820.
27. Godlewski J., et al. “MicroRNA-451 Regulates LKB1/AMPK Signaling and Allows Adaptation to Metabolic Stress in Glioma Cells”. Molecular Cell 37 (2010): 620-632.

Citation

Citation: Marianna Papadaki., et al. “Impact of Circulating miRNAs in Cutaneous T-cell Lymphoma Diagnosis: miR-146a and miR-26a as Promising Diagnostic Biomarkers”.Acta Scientific Medical Sciences 6.4 (2022): 90-99.

Copyright

Copyright: © 2022 Marianna Papadaki., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.