Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2013 Jun 25;8(6):e66778. doi: 10.1371/journal.pone.0066778. Print 2013.
Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors.
MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features.
Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets.
Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.
唾液腺腺样囊性癌（ACC）是一种罕见的、持续进展的恶性肿瘤。与 ACC 肿瘤发生相关的分子事件尚未完全了解。多种实体瘤的发生与可变 microRNAs（miRNA）相关，但 ACC 中并非如此。为了研究 miRNA 与 ACC 的发生和/或进展的相关性，我们对原发性 ACC 标本和配对的正常样本进行了比较分析，并对唾液腺标准品进行了汇总分析，并将结果与临床病理因素相关联，并在另一组 30 个肿瘤中验证了选定的 miRNA。
使用 miRNA 阵列平台来鉴定靶 miRNA，并对数据进行信息学和统计学的相互关系分析。结果还与 MYB-NFIB 融合状态和临床病理特征一起收集。
与正常表达相比，ACC 中差异失调的 miRNA 特征明显。在 MYB-NFIB 融合阳性和阴性 ACC 之间，miRNA 的表达没有显著差异。在 ACC 中高度失调的 miRNA 中，miR-17 和 miR-20a 的过表达与筛选和验证组的不良预后显著相关。
我们的研究表明，miR-17-92 的上调可能在 ACC 的生物学中发挥作用，并可能成为未来治疗研究的潜在靶点。
