Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas
Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas
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DOI：
10.1111/j.1349-7006.2009.01385.x
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Yaegashi, Nobuo
中科院分区：
文献类型：
--
作者：
Hiroki, Eri;Akahira, Jun-ichi;Yaegashi, Nobuo
本研究旨在确定子宫内膜浆液性腺癌中microRNAs （miRNAs）的表达谱，并研究miRNA表达与临床结果之间的关系。在2001年1月至2006年12月期间，21名诊断为子宫内膜浆液性腺癌的患者被纳入研究。采用miRNA芯片和qRT-PCR检测miRNA表达谱。miRNA表达水平与临床病理变量和生存率相关。与正常子宫内膜相比，子宫内膜浆液性腺癌中共有120种mirna差异表达。其中，54个mirna下调（> 2倍），包括miR-101、miR-10b*、miR-152和miR-29b，其余的上调（> 2倍），包括miR-200a、miR-200b和miR-205。miR-10b*、miR-29b、miR-455-5p的表达降低与血管侵袭相关（P = 0.048、P = 0.013、P = 0.032）。单因素分析显示，miR-101、miR-10b*、miR-139-5p、miR-152、miR-29b和miR-455-5p的低表达与总生存期差显著相关（P < 0.05）， miR-152、miR-29b和miR-455-5p的低表达与无病生存期差显著相关（P < 0.05）。多因素分析显示，miR-152表达降低（P = 0.021）是影响总生存的独立危险因素，miR-101表达降低（P = 0.016）和miR-152表达降低（P = 0.010）是影响无病生存的独立危险因素。此外，转染miR-101或miR-152前体到子宫内膜浆液性癌细胞系中可以抑制细胞生长（P < 0.0001和P = 0.01）。此外，环氧化酶-2 （COX-2）的强阳性免疫反应性与miR-101的下调显著相关（P = 0.035）。这些发现提示mirna的失调与子宫内膜浆液性腺癌患者预后不良有关。（癌症科学2009）。
This study aimed to determine the expression profiles of microRNAs (miRNAs) in endometrial serous adenocarcinoma and to examine the association between miRNA expression and clinical outcomes. Twenty-one patients diagnosed with endometrial serous adenocarcinoma between January 2001 and December 2006 were enrolled. miRNA expression profiles were examined using miRNA microarray and qRT-PCR. miRNA expression levels were correlated with clinicopathological variables and survival rates. A total of 120 miRNAs were differentially expressed in endometrial serous adenocarcinoma compared to normal endometria. Of these, 54 miRNAs were down-regulated (> 2-fold), including miR-101, miR-10b*, miR-152, and miR-29b, and the remainder were up-regulated (> 2-fold), including miR-200a, miR-200b, and miR-205. Decreased expression of miR-10b*, miR-29b, and miR-455-5p was correlated with vascular invasion (P = 0.048, P = 0.013, and P = 0.032, respectively). Univariate analysis revealed that lower expression of miR-101, miR-10b*, miR-139-5p, miR-152, miR-29b, and miR-455-5p was significantly correlated with poor overall survival (P < 0.05), and reduced expression of miR-152, miR-29b, and miR-455-5p was significantly correlated with poor disease-free survival (P < 0.05). Multivariate analysis demonstrated that decreased expression of miR-152 (P = 0.021) was a statistically independent risk factor for overall survival, and decreased expression levels of miR-101 (P = 0.016) and miR-152 (P = 0.010) were statistically independent risk factors for disease-free survival. In addition, transfection of miR-101 or miR-152 precursors into an endometrial serous carcinoma cell line inhibited cell growth (P < 0.0001 and P = 0.01, respectively). Moreover, strong positive immunoreactivity of cyclooxygenase-2 (COX-2) was significantly correlated with down-regulation of miR-101 (P = 0.035). These findings suggest that the dysregulation of miRNAs is associated with the poor prognosis in endometrial serous adenocarcinoma patients. (Cancer Sci 2009).