Abstract

Primary cutaneous T-cell lymphomas (CTCL) affect the skin and tend to transform and spread. CTCL involves primarily the Mycosis fungoides (MF) and more aggressive Sezary syndrome (SS). Oncogenic microRNAs (miRs) are stable epigenetic inhibitors often deregulated in the tumour and detectable as biomarkers in non-cellular fractions of peripheral blood. The tumour-specific expression of miR-155, miR-203, and miR-205 was shown to correctly diagnose CTCL. We herein asked whether these microRNAs can be used as plasma biomarkers for clinical CTCL monitoring. Patients with CTCL (n = 10) and controls with non-malignant conditions (n = 11) repeatedly donated plasma samples every ca. five months. MicroRNAs were detected in the plasma samples by specifically-primed RT-PCR followed by multivariate analyses of the miR expression dynamics. We herein established the plasma miR-classifier for detecting CTCL based on the miR-155 upregulation and miR-203/miR-205 downregulation with 100% specificity and 94% sensitivity. The 3-miR-score in the consecutive samples coincided with the clinical outcome of MF and SS patients such as the therapy response or changes in the clinical stage or tumor size. Quantitation of the selected microRNAs in plasma is a specific and straightforward approach for evaluating CTCL outcome representing, thus, a valuable tool for CTCL diagnostics and therapy response monitoring.

Highlights

  • Primary cutaneous T-cell lymphomas (CTCL) affect the skin in form of lesions that tend to transform and spread into lymph nodes, organs or blood

  • It is established for some cancers that oncomiRs are detectable in non-cellular fractions of peripheral blood

  • We analysed the data with the principal component analysis (PCA) and observed that samples from CTCL became separated from benign lesions (BL) and normal individuals (Figure 1B, left)

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Summary

Introduction

Primary cutaneous T-cell lymphomas (CTCL) affect the skin in form of lesions that tend to transform and spread into lymph nodes, organs or blood. CTCL is a heterogeneous group of lymphomas that in up to 3/4 of cases present as Mycosis fungoides (MF) Another form of CTCL with overlapping and aggressive features is represented by the Sezary syndrome (SS). Another goal is to evolve sensitive diagnostic and monitoring techniques to distinguish CTCL from benign lesions and to assess therapeutic responses and predict/confirm progression. Such approach may be very beneficial for all CTCL patients, but especially for those with advanced-stage disease potential resulting in nodal, visceral, or blood involvement. The treatment of CTCL does not usually lead to long-lasting complete remission

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