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08.16 Mir200B-5p expression in minor salivary glands (msg): a possible predictor of lymphoma development in sjögren’s syndrome (ss)
  1. Efstathia K. Kapsogeorgou,
  2. Aristea Papageorgiou,
  3. Michael Voulgarelis,
  4. Athanasios G. Tzioufas
  1. Department of Pathophysiology and Academic Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Greece

Abstract

Background-aim Our preliminary data suggested that miR200b-5p miRNA expression may be down-regulated in the MSG-tissues of SS patients with MALT-lymphoma (Gourzi et al., Clin Exp Immunol. 2015). Herein, we sought to investigate whether low miR200b-5p MSG-levels are associated with SS-related lymphomas and their possible prognostic value for lymphoma development.

Methods miR200b-5p expression was analysed by quantitative real-time PCR in total RNA from MSG-tissues from 77 SS-patients and 9 patients with chronic sialadenitis associated with sarcoidosis, HCV (4-each) or HBV infection (1 who was also diagnosed with MALT-lymphoma). SS-patients included 28 that did not develop lymphoma during follow-up (without lymphoma; median follow-up time since biopsy performance, range: 6 years, 1–12.75 years), 17 that developed lymphoma in the future (prelymphoma; median follow-up time till lymphoma diagnosis, range: 3.59 years, 0.42–8.5 years, 15-MALT, 2-NMZL, 1-DLCBL) and 31 with SS-associated lymphoma at the time of biopsy (lymphoma; 24-MALT, 2-NMZL, 2-DLCBL,1-BALT, 1-LP and 1-SLL). In 15 cases, we had sequential MSG-samples from prelymphoma patients who transitioned to lymphoma (12-MALT, 2-NMZL, 1-DLCBL).

Results Tukey’s multiple comparison revealed that miR200b-5p levels were significantly down-regulated in MSG tissues of prelymphoma and lymphoma SS-patients (mean relative expression±SE: 0.37±0.10 and 0.26±0.06, respectively) compared to SS-patients without lymphoma (0.67±0.07; p≤0.05 and p≤0.0001 for pre- and lymphoma, respectively) or non-SS sialadenitis (0.85±0.28, p≤0.05 and p≤0.01, respectively). The expression of miR200b-5p was not found to differ between patients with SS without lymphoma and non-SS sialadenitis, or SS-associated pre-lymphoma and lymphoma. The miR200b-5p expression was not found to change significantly over transition to lymphoma. The miR200b-5p expression levels were negatively correlated with the biopsy focus score (r: −0.6550, p<0.0001), whereas they were not associated with the site or the number of involved sites, the type or the stage of lymphoma.

Conclusions The significantly lower expression of miR200b-5p in the MSG tissues of patients with SS-associated prelymphomas and lymphomas implicates it in SS-lymphomagenesis. In addition, the significantly lower levels of miR200b-5p in prelymphoma-MSGs suggests that it can serve as a prognostic marker for future lymphoma development. The prognostic value of miR200b-5p in SS-associated lymphomas, the expressing cell types and molecular pathways that regulates are under investigation.

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