Background/Purpose:  The miRNAs of the miR-200 family are critical regulators of oncogene and tumor suppressor genes. A preliminary study of several miRNAs in the MSGs of SS patients, including 4 patients with MALT lymphoma, suggested that the expression of miR200b-5p may be down-regulated in lymphoma (Gourzi et al., Clin Exp Immunol. 2015). The aim of our study is to validate the down-regulation of miR200b-5p in MSGs of patients with SS-related lymphoma and to investigate whether its expression is deregulated before lymphoma development.

Methods:  miR200b-5p expression was analyzed by quantitative real-time PCR in total RNA from MSG tissues obtained from 74 SS patients and 9 patients with non-SS sialadenitis associated with sarcoidosis, HCV infection (4 each) or HBV (1 that was also diagnosed with MALT lymphoma). The SS patients group included 28 patients that did not develop lymphoma during follow up (without lymphoma; median follow up time since biopsy performance, range: 6yrs, 1-12.75yrs), 17 patients that developed lymphoma in the future (prelymphoma; median follow up time till lymphoma diagnosis, range: 3.67yrs, 0.42-8.5yrs, 13 MALT, 2 NMZL, 1 DLCBL and 1 SLL) and 30 patients with SS-associated lymphoma at the time of biopsy (lymphoma; 23 MALT, 2 NMZL, 2 DLCBL,1 BALT, 1 LP and 1 SLL). Prelymphoma and lymphoma MSG samples were obtained from the same SS patients in 13 cases (10 MALT, 2 NMZL and 1 DLCBL). Differences in miR200b-5p expression levels among the studied groups was analyzed by Tukey’s multiple comparison test, whereas repeated measures analysis was employed to evaluate whether miR200b-5p expression changes over lymphoma development (in the prelymphoma and lymphoma MSGs from the 13 patients).

Results:  miR200b-5p was significantly down-regulated in MSG tissues of prelymphoma and lymphoma SS patients (mean relative expression±SE: 0.38±0.10 and 0.27±0.06, respectively) compared to SS patients without lymphoma (0.77±0.12; p≤0.05 and p≤0.001 for pre- and lymphoma, respectively) or non-SS sialadenitis (0.82±0.25, 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 pre-lymphoma and lymphoma SS patients. Interestingly, low expression of miR200b-5p (0.17) was detected in the MSG tissue obtained from the HBV-infected patient that had MALT lymphoma. Finally, the expression levels of miR200b-5p were not found to differ in prelymphoma and lymphoma tissues of the 13 patients that had both samples.

Conclusion: The significantly lower expression of miR200b-5p in SS associated MALT lymphoma implicates it in lymphomagenesis, whereas its significant down-regulation in prelymphoma MSGs suggests that miR200b-5p can serve as a prognostic marker for future lymphoma development. The cell types that express miR200b-5p and the molecular pathways that regulates are under investigation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mir200b-5p-expression-in-minor-salivary-glands-msg-a-possible-predictor-of-lymphoma-development-in-sjogrens-syndrome-ss/