目的通过比较甲状腺良恶性肿瘤组织样本中HYAL2基因CpG位点甲基化水平的差异,评估其作为甲状腺癌鉴别诊断分子标志物的潜在价值。方法采用飞行时间质谱检测190对甲状腺乳头状癌(PTC)病例和年龄、性别配对的甲状腺腺瘤中HYAL2基因启动子...目的通过比较甲状腺良恶性肿瘤组织样本中HYAL2基因CpG位点甲基化水平的差异,评估其作为甲状腺癌鉴别诊断分子标志物的潜在价值。方法采用飞行时间质谱检测190对甲状腺乳头状癌(PTC)病例和年龄、性别配对的甲状腺腺瘤中HYAL2基因启动子区域CpG位点的甲基化水平。采用免疫组化检测另外55对匹配的甲状腺良恶性肿瘤患者的HYAL2蛋白表达水平。Logistic回归分析用于评估甲基化水平每降低10%与早期PTC之间的关联并计算比值比(OR)。受试者工作特征曲线及曲线下面积(AUC)用于评估HYAL2基因特定CpG位点甲基化水平改变作为分子标志物的效能。结果HYAL2_CpG_3位点低甲基化与早期PTC显著相关(OR=1.51,P=0.001),且该关联在Ⅰ期PTC中依旧显著(OR=1.42,P=0.007)。年龄分层分析显示HYAL2_CpG_3甲基化水平降低与早期PTC关联在年龄小于50岁的人群中显著高于高年龄组(OR:1.89 vs 1.37;P<0.05),且低年龄组人群中AUC最高,为0.787。免疫组化结果显示早期PTC中HYAL2蛋白表达水平显著高于甲状腺良性肿瘤。结论HYAL2基因启动子区域甲基化水平改变与早期PTC的关联,并为DNA甲基化改变作为甲状腺良恶性肿瘤鉴别诊断的标志物提供了新思路。展开更多
The sheep genome harbours approximately 20 copies of endogenous beta-retroviruses （enJSRVs）, and circumstantial evidence suggests that enJSRVs might play a role in mammalian reproduction, particularly placental morp...The sheep genome harbours approximately 20 copies of endogenous beta-retroviruses （enJSRVs）, and circumstantial evidence suggests that enJSRVs might play a role in mammalian reproduction, particularly placental morphogenesis. This study was aimed to assess the expression of mRNAs of an enJSRV and its receptor, HYAL2, in the uterus and conceptuses of Mongolian ewes throughout gestation, using real-time reverse transcription polymerase chain reaction and in situ hybridization analysis. The results showed that enJSRV and HYAL2 mRNAs were found to be expressed throughout gestation in the endometrium, chorion, placenta, and conceptus. The enJSRV mRNA was most abundant in the placenta on day 90 of pregnancy, in the endometrium on day 30 and 50, and in the chorion on day 70 and 110. However, HYAL2 mRNA was most abundant in the endometrium on day 30. These differences were all significantly different from each other （P〈0.01）. In situ hybridization showed that enJSRV and HYAL2 mRNAs were specifically expressed in endometrial luminal epithelium and glandular epithelium, trophoblastic giant binucleated cells （BNCs）, endometrial caruncles, placental cotyledons, stroma, trophectoderm, as well as multinucleated syncytia of the placenta and blood vessel endothelial cells. Collectively, little is known about the molecular mechanisms by which trophoblastic differentiation and multinucleated syncytia formation are regulated by enJSRVs. However, the temporal and spatial distributions of enJSRV expression in the uterus and conceptus indicate that differentiation of BNCs and the formation of a multinucleated syncytiotrophoblast involve enJSRV and possibly its cellular receptor, HYAL2. Therefore, enJSRV and HYAL2 appear to play important roles in the female reproductive physiology in this breed of sheep.展开更多
文摘目的通过比较甲状腺良恶性肿瘤组织样本中HYAL2基因CpG位点甲基化水平的差异,评估其作为甲状腺癌鉴别诊断分子标志物的潜在价值。方法采用飞行时间质谱检测190对甲状腺乳头状癌(PTC)病例和年龄、性别配对的甲状腺腺瘤中HYAL2基因启动子区域CpG位点的甲基化水平。采用免疫组化检测另外55对匹配的甲状腺良恶性肿瘤患者的HYAL2蛋白表达水平。Logistic回归分析用于评估甲基化水平每降低10%与早期PTC之间的关联并计算比值比(OR)。受试者工作特征曲线及曲线下面积(AUC)用于评估HYAL2基因特定CpG位点甲基化水平改变作为分子标志物的效能。结果HYAL2_CpG_3位点低甲基化与早期PTC显著相关(OR=1.51,P=0.001),且该关联在Ⅰ期PTC中依旧显著(OR=1.42,P=0.007)。年龄分层分析显示HYAL2_CpG_3甲基化水平降低与早期PTC关联在年龄小于50岁的人群中显著高于高年龄组(OR:1.89 vs 1.37;P<0.05),且低年龄组人群中AUC最高,为0.787。免疫组化结果显示早期PTC中HYAL2蛋白表达水平显著高于甲状腺良性肿瘤。结论HYAL2基因启动子区域甲基化水平改变与早期PTC的关联,并为DNA甲基化改变作为甲状腺良恶性肿瘤鉴别诊断的标志物提供了新思路。
基金funded by the National Natural Science Foundation of China (30960271 and 31160493)the doctor fund project of Ministry of Education of China(20111515110008)
文摘The sheep genome harbours approximately 20 copies of endogenous beta-retroviruses （enJSRVs）, and circumstantial evidence suggests that enJSRVs might play a role in mammalian reproduction, particularly placental morphogenesis. This study was aimed to assess the expression of mRNAs of an enJSRV and its receptor, HYAL2, in the uterus and conceptuses of Mongolian ewes throughout gestation, using real-time reverse transcription polymerase chain reaction and in situ hybridization analysis. The results showed that enJSRV and HYAL2 mRNAs were found to be expressed throughout gestation in the endometrium, chorion, placenta, and conceptus. The enJSRV mRNA was most abundant in the placenta on day 90 of pregnancy, in the endometrium on day 30 and 50, and in the chorion on day 70 and 110. However, HYAL2 mRNA was most abundant in the endometrium on day 30. These differences were all significantly different from each other （P〈0.01）. In situ hybridization showed that enJSRV and HYAL2 mRNAs were specifically expressed in endometrial luminal epithelium and glandular epithelium, trophoblastic giant binucleated cells （BNCs）, endometrial caruncles, placental cotyledons, stroma, trophectoderm, as well as multinucleated syncytia of the placenta and blood vessel endothelial cells. Collectively, little is known about the molecular mechanisms by which trophoblastic differentiation and multinucleated syncytia formation are regulated by enJSRVs. However, the temporal and spatial distributions of enJSRV expression in the uterus and conceptus indicate that differentiation of BNCs and the formation of a multinucleated syncytiotrophoblast involve enJSRV and possibly its cellular receptor, HYAL2. Therefore, enJSRV and HYAL2 appear to play important roles in the female reproductive physiology in this breed of sheep.
