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.