Abstract
AbstractMycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma. The disease often takes an indolent course, but in approximately one-third of the patients, the disease progresses to an aggressive malignancy with a poor prognosis. At the time of diagnosis, it is impossible to predict which patients develop severe disease and are in need of aggressive treatment. Accordingly, we investigated the prognostic potential of microRNAs (miRNAs) at the time of diagnosis in MF. Using a quantitative reverse transcription polymerase chain reaction platform, we analyzed miRNA expression in diagnostic skin biopsies from 154 Danish patients with early-stage MF. The patients were subdivided into a discovery cohort (n = 82) and an independent validation cohort (n = 72). The miRNA classifier was built using a LASSO (least absolute shrinkage and selection operator) Cox regression to predict progression-free survival (PFS). We developed a 3-miRNA classifier, based on miR-106b-5p, miR-148a-3p, and miR-338-3p, which successfully separated patients into high-risk and low-risk groups of disease progression. PFS was significantly different between these groups in both the discovery cohort and the validation cohort. The classifier was stronger than existing clinical prognostic factors and remained a strong independent prognostic tool after stratification and adjustment for these factors. Importantly, patients in the high-risk group had a significantly reduced overall survival. The 3-miRNA classifier is an effective tool to predict disease progression of early-stage MF at the time of diagnosis. The classifier adds significant prognostic value to existing clinical prognostic factors and may facilitate more individualized treatment of these patients.
Highlights
Mycosis fungoides (MF) is an extranodal non-Hodgkin lymphoma representing the most prevalent entity among cutaneous T-cell lymphomas (CTCLs).[1]
In order to subdivide the patients into a highand low-risk group of disease progression, we set the risk score cutoff level to 21.44 so that the number of high-risk individuals in the discovery cohort matched the number of individuals who progressed
Performing univariate analysis, we found that the 3-miRNA classifier was a stronger predictor of disease progression than the miRNAs individually, and that it was significantly stronger than existing clinical prognostic factors, including sex, age, patch/plaque T stage (T1a/T2a vs T1b/T2b), and the cutaneous lymphoma international prognostic index (CLIPi) score (Table 2)
Summary
Mycosis fungoides (MF) is an extranodal non-Hodgkin lymphoma representing the most prevalent entity among cutaneous T-cell lymphomas (CTCLs).[1]. Current practice involves clinical monitoring and aggressive treatment at signs of disease progression; and existing treatment guidelines are based on the disease stage of MF in general rather than the individual patient’s risk of disease progression.[8] Prognostic stratification of patients with early-stage MF seems warranted. Genetic aberrations and epigenetic changes have been associated with disease progression and survival in patients with MF, but independently validated prognostic molecular classifiers have not yet been developed.[9,10,11] Recently, a prognostic clinical index, cutaneous lymphoma international prognostic index (CLIPi), was proposed to classify early- and late-stage MF into low, intermediate, and high risk of disease progression and reduced survival.[12] CLIPi is based on a combination of clinical variables that were associated with disease progression and/or reduced survival in a multivariable analysis in a large cohort of patients with MF and Sezary syndrome.[5]
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