Dental Research Center, Dentistry Research Institute, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, Tehran, Iran.
Head Neck Pathol. 2022 Dec;16(4):1134-1145. doi: 10.1007/s12105-022-01475-0. Epub 2022 Aug 18.
Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need for specifying prognostic biomarkers to identify patients who are in need of more intensive and prolonged follow-ups. This study aimed to assess the mucin 1 (MUC1) expression level and its potential regulatory microRNAs in salivary gland MEC and their prognostic potentials.
The expression of MUC1 in salivary gland MEC tissues was assessed in 47 samples using immunohistochemistry. Related microRNA (miR-145 and miR-21) were evaluated using quantitative Reverse Transcription PCR. The associations between MUC1 and microRNAs expressions and clinicopathological parameters were investigated.
MUC1 expression levels positively correlated with histologic grade (p < 0.001), clinical stage (p = 0.04), risk of nodal metastasis (p = 0.02), as well as the likelihood of opting for radical treatment (p = 0.01). Increased expression of miR-21 (p < 0.001) and decreased expression of miR-145 (p < 0.001) were observed in MECs compared to normal salivary gland tissue. MiR-145 negatively (p = 0.01) and miR-21 positively (p = 0.01) correlated with MUC1 overexpression. Based on the univariate cox proportional hazard model, histologic grade and MUC1 expression level were significantly associated with disease-free, cancer-specific, and overall survival. However, the multivariable cox proportional hazard model indicated tumor grade as the only prognostic factor associated with disease-free survival.
Our results support the tumor suppressor role of miR-145 and the oncogenic role of miR-21 in salivary gland MEC. Also, MUC1 and miR-145 overexpression, as well as miR-21 suppression, show promising association with histologic tumor grade and clinical stage.
唾液腺癌黏液表皮样癌(MEC)在接受常规治疗后局部和远处转移的风险相当高。显然需要确定预后生物标志物,以识别需要更强化和延长随访的患者。本研究旨在评估唾液腺癌 MEC 中粘蛋白 1(MUC1)的表达水平及其潜在的调节 microRNA,并评估其预后潜力。
采用免疫组织化学法检测 47 例唾液腺癌 MEC 组织中 MUC1 的表达。采用定量逆转录 PCR 评估相关 microRNA(miR-145 和 miR-21)。研究 MUC1 与 microRNAs 表达与临床病理参数之间的关系。
MUC1 表达水平与组织学分级(p<0.001)、临床分期(p=0.04)、淋巴结转移风险(p=0.02)以及选择根治性治疗的可能性(p=0.01)呈正相关。与正常唾液腺组织相比,MEC 中 miR-21 的表达增加(p<0.001),miR-145 的表达降低(p<0.001)。miR-145 与 MUC1 过表达呈负相关(p=0.01),miR-21 与 MUC1 过表达呈正相关(p=0.01)。根据单因素 cox 比例风险模型,组织学分级和 MUC1 表达水平与无病生存、癌症特异性和总生存显著相关。然而,多变量 cox 比例风险模型表明,肿瘤分级是与无病生存相关的唯一预后因素。
我们的研究结果支持 miR-145 的肿瘤抑制作用和 miR-21 在唾液腺癌 MEC 中的致癌作用。此外,MUC1 和 miR-145 的过表达以及 miR-21 的抑制与组织学肿瘤分级和临床分期有很好的相关性。