卵巢癌中 microRNA 的表达及其与临床病理特征的相关性。
MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features.
机构信息
Department of Pathology, College of Medicine, The Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea.
出版信息
World J Surg Oncol. 2012 Aug 27;10:174. doi: 10.1186/1477-7819-10-174.
BACKGROUND
MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.
METHODS
We measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.
RESULTS
Expression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu.
CONCLUSIONS
Aberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.
背景
已知 miRNA（microRNA）表达在卵巢癌中失调。然而，关于良性或交界性卵巢肿瘤的 miRNA 表达模式以及与组织学类型、分级或临床分期相关的差异 miRNA 表达模式的资料有限。我们定义了正常、良性、交界性和恶性卵巢肿瘤组织中的 miRNA 表达模式，并探讨了经常失调的 miRNA 与临床病理发现、治疗反应、生存以及与卵巢癌中 Her-2/neu 状态的关系。
方法
我们使用 Taqman 实时 PCR 测定法测量了 171 个福尔马林固定、石蜡包埋的卵巢组织块和 6 个人类正常卵巢表面上皮（HOSE）细胞系中的 9 个 miRNA（miR-181d、miR-30a-3p、miR-30c、miR-30d、miR-30e-3p、miR-368、miR-370、miR-493-5p、miR-532-5p）的表达。使用免疫组织化学分析评估了卵巢癌（n=109 例）中的 Her-2/neu 过表达。
结果
miR-30c、miR-30d、miR-30e-3p 和 miR-370 的表达在癌组织与良性卵巢组织以及癌组织与交界性组织之间存在显著差异。另外三个 miRNA（miR-181d、miR-30a-3p、miR-532-5p）在交界性组织与癌组织之间存在显著差异。miR-532-5p 在交界性组织中的表达明显低于良性组织。在卵巢癌中，miR-30a-3p、miR-30c、miR-30d 和 miR-30e-3p 的表达在黏液性和透明细胞样本中最低，在高分化样本中最高。miR-30a-3p 的表达在分化良好的肿瘤中高于分化不良的肿瘤（P=0.02），miR-370 的表达在 I/II 期样本中高于 III/IV 期样本（P=0.03）。在多变量分析中，miR-181d、miR-30c、miR-30d 和 miR-30e-3p 的高表达与无病或总生存显著相关。最后，miR-30c、miR-30d、miR-30e-3p 和 miR-532-5p 的低表达与 Her-2/neu 的过表达显著相关。
结论
miRNA 的异常表达在卵巢肿瘤中很常见，提示 miRNA 参与了卵巢肿瘤的发生。它们与卵巢癌的组织学、临床分期、生存和癌基因表达有关。
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