摘要目的 探讨典型子宫内膜样癌组织微小RNA(miRNA)的表达特点及与子宫内膜癌相关分子改变的内在关联性及其临床意义.方法 以TaqMan低密度芯片分析2例子宫内膜样癌组织miRNA的表达特点.筛选表达显著差异的miRNA,采用即时荧光定量聚合酶链反应技术检测73例子宫内膜癌组织中这些miRNA的表达.免疫组织化学法检测miRNA的预测靶基因PTEN表达.结果 (1) miRNA表达谱分析显示相对于增殖期内膜,典型Ⅰ型癌组织共有47个miRNA存在差异表达,其中26个表达降低,21个表达升高.(2)进一步筛选8种miRNA验证其表达:8种miRNA在58例Ⅰ型癌中的表达与表达谱结果一致,其中表达升高的3种miRNA(miR-141、miR-200a、miR-205)及表达降低的两种miRNA(miR-143和miR-145),差异均有统计学意义(P＜0.05),但此5种miRNA在Ⅱ型内膜癌中变化不显著.(3)Ⅰ型内膜癌中miR-141、miR-200a高表达组的PTEN失表达率更高,且miR-200a与PTEN表达呈负相关(P＜0.05).结论 Ⅰ型子宫内膜癌有相对特异的miRNA表达谱；miR-200a、miR-205、miR-141、miR-143、miR-145在Ⅰ型癌中变化显著,但在Ⅱ型癌中变化不显著,提示Ⅰ/Ⅱ型癌发病中发挥作用的miRNA不尽相同.Ⅰ型癌中miR-141和miR-200a可能通过对抑癌基因PTEN的靶向调控,参与子宫内膜癌的形成及演进.

abstractsObjective To determine the microRNA (miRNA) expression signature and its clinical significance in endometrioid carcinoma (EC).Methods The miRNA profiles were analyzed by miRNA microarray in 73 cases of EC.The expression level of the eight selected miRNAs were measured by real-time fluorescent quatitative PCR(qRT-PCR).Immunohistochemistry (IHC) was performed to assess the status of PTEN,a potential target of the selected miRNAs.Results (1) Using TaqMan low-density arrays,47 miRNAs that differed between EC and normal controls were identified,including 26 down-regulated and 21 up-regulated miRNAs.(2) To confirm the miRNA expression pattern in type Ⅰ EC,the expression levels of the eight selected miRNAs were evaluated in a new set of 58 cases of type Ⅰ EC by individual miRNA qRT-PCR assays.Three miRNAs (miR-141,miR-200a,miR-205) were up-regulated and two miRNAs (miR-143,miR-145) were down-regulated.These were significantly differentially expressed in type Ⅰ EC and normal controls (P ＜ 0.05),whereas such difference was not present in type Ⅱ tumors compared to normal controls.(3) In type Ⅰ EC,loss of PTEN was more frequent in the miR-141 or miR-200a up-regulated subgroups,and the correlation between the PTEN and miR-200a status in type Ⅰ tumors was statistically significant (P ＜0.05).Conclusions EC may have a unique miRNA expression profile.The expression levels of the five miRNAs (miR-141,miR-200a,miR-205,miR-143,miR-145) are significantly deregulated in type Ⅰ EC compared to normal control but not in type Ⅱ tumors.The findings suggest that the miRNAs related to type Ⅰ and type Ⅱ EC might be different.PTEN might be a potential target of miR-141 and miR-200a in endometrial carcinogenesis.