Comparison of microRNA profiles between benign and malignant salivary gland tumors in tissue, blood and saliva samples: a prospective, case-control study

Abstract Introduction: Salivary gland tumors (SGTs) are rare head and neck malignancies consisting of a spectrum of tumors with different biological behaviors. Objective: In this study we aimed to find out differential expression of microRNA profiles between benign and malignant SGTs. Methods: We investigated the possible role of 95 microRNAs in the 20 patients with salivary gland tumors with comparison of 17 patients without malignancy or salivary gland diseases. Sixteen of the tumors were benign (seven pleomorphic adenomas, nine Warthin tumors), four of them were malignant (two squamous cell carcinomas, one high grade mucoepidermoid carcinoma, one adenocarcinoma). Serum and saliva samples were collected from both patients and control group. Tissue samples of tumor masses were also collected from patient group. Results: Among studied microRNAs miR-21, miR-23a, miR-27a, miR-223, miR-125b, miR-126, miR-146a, miR-30e were down regulated in the benign group compared to control group in the serum samples (p-values are 0.04, 0.00005, 0.00005, 0.0022, 0.031, 0.00008, 0.044, and 0.0007, respectively). When tissue samples were studied miR-21, miR-31, miR-199a-5p, miR-146b, miR-345 were up-regulated in the malignant group compared to benign group (p values are 0.006, 0.02, 0.013, 0.013, 0.041, respectively). miR-30e showed statistically significant up-regulation in malignant tumor group's plasma samples compared to benign group (p = 0.034). There was no statistically significant difference in saliva samples between groups. Conclusion: Our results showed that different microRNAs may play role in salivary tumor pathogenesis according to biological behavior. Although there was no difference in saliva samples between groups, according to tissue and serum samples miR-21 and 30e may have an important role; since they were down-regulated in benign tumors whereas up-regulated in malignant ones.

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Resumo Introdução: Os tumores da glândula salivar (TGS) são lesões malignas raras de cabeça e pescoçoque consistem em um espectro de tumores com diferentes comportamentos biológicos. Objetivo: Neste estudo, tivemos como objetivo identificar a expressão diferencial de perfis demicroRNA entre TGS benignos e malignos. Método: Investigamos a possível participação de 95 microRNA em 20 pacientes com tumoresde glândulas salivares comparados com 17 pacientes sem doença maligna ou doenças das glân-dulas salivares; 16 dos tumores eram benignos (sete adenomas pleomórficos, nove tumores deWarthin), quatro eram malignos (dois carcinomas espinocelulares, carcinoma mucoepidermoidede alto grau, um adenocarcinoma). As amostras de soro e saliva foram coletadas de pacien-tes e do grupo controle. Amostras de tecido dos tumores também foram colhidas do grupo depacientes com tumores. Resultados: Entre os microRNA estudados, miR-21, miR-23a, miR-27a, miR-223, miR-125b, miR-126, miR-146a, miR-30e foram infrarregulados no grupo benigno em comparação com o grupocontrole nas amostras do soro (os valores de p são 0,04, 0,00005, 0,00005, 0,0022, 0,031,0,00008, 0,044 e 0,0007, respectivamente). Quando as amostras de tecido foram estudadas,miR-21, o miR-31, o miR-199-5p, miR-146b, o miR-345 foram suprarregulados no grupo malignoem relação ao grupo benigno (valores de p são 0,006, 0,02, 0,013, 0,013, 0,041, respectiva-mente). O miR-30e apresentou suprarregulação estatisticamente significativa em amostras deplasma do grupo de tumor maligno em relação ao grupo benigno (p = 0,034). Não houve diferençaestatisticamente significativa em amostras de saliva entre os grupos. Conclusão: Nossos resultados mostraram que diferentes microRNA podem desempenhar umpapel na patogenia do tumor salivar de acordo com o comportamento biológico. Embora nãotenha havido diferença em amostras de saliva entre os grupos, de acordo com as amostras detecido e de soro, miR-21 e 30e podem ter um papel importante, já que foram infrarreguladosnos tumores benignos enquanto suprarregulados nos tumores malignos.

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