TTF-1和PTEN基因在子宫内膜癌早期病变中的表达意义
Significance of Thyroid Transcription Factor-1 and Phosphatase and Tensin Homolog Genes Expression in Early Endometrial Cancer
-
摘要: 目的 分析甲状腺转录因子-1 (TTF-1) 和磷酸酶与张力蛋白同源物 (PTEN) 基因在子宫内膜癌早期病变中的表达意义.方法 选择子宫内膜癌41例、增生性子宫内膜38例和正常子宫内膜13例, 采用荧光定量PCR法 (RT-PCR) 检测3种子宫内膜中TTF-1和PTEN mRNA表达量, 分析其与临床病理特征的关系;RT-PCR法检测3种子宫内膜中mi R-135b、mi R-125b和Snail mRNA表达量, 分析其与TTF-1和PTEN mRNA表达量的相关性.结果 子宫内膜癌组织中TTF-1和PTEN mRNA表达量显著低于其他2组, 正常子宫内膜组织中表达量最高, 差异有统计学意义 (P<0.05) .绝经与否、腺癌和鳞癌间TTF-1和PTEN mRNA表达水平比较, 差异无统计学意义 (P>0.05) ;FIGO分期增加、肌层浸润增加、盆腔淋巴结转移的TTF-1和PTEN mRNA表达水平明显降低, 差异有统计学意义 (P<0.05) .子宫内膜癌中mi R-135b mRNA的表达水平显著高于其他2组, 正常子宫内膜中最低;mi R-125b和Snail mRNA的表达水平显著低于其他2组, 正常子宫内膜中最高;差异有统计学意义 (P<0.05) .TTF-1和PTEN mRNA表达量与mi R-135b mRNA表达量呈负相关, 与mi R-125b和Snail mRNA表达量呈正相关 (P<0.05) .ROC模型得出, TTF-1 mRNA诊断子宫内膜癌的敏感性86.5%, 特异性84.2%, 准确性0.823, 95%CI=0.7620.921, P=0.012;PTEN mRNA诊断子宫内膜癌的敏感性85.3%, 特异性83.6%, 准确性0.842, 95%CI=0.7850.936, P=0.010.结论 TTF-1和PTEN基因可作为子宫内膜癌早期诊断的分子标志物, 与临床特征密切相关, 可能通过调控肿瘤细胞增殖活性影响肿瘤进程.Abstract: Objective To study the significance of thyroid transcription factor-1 (TTF-1) and phosphatase and tensin homolog (PTEN) genes expression in early endometrial cancer. Methods A total of 41 consecutives as endometrial cancer, 38 patients with hyperplastic endometrium and 13 cases of normal endometrium were enrolled, then we detected the levels of TTF-1 and PTEN mRNA in the three endometrium tissues by fluorescent quantitative PCR (RT-PCR) , and analyzed the relationship between them and clinicopathological features;the correlation of TTF-1 and PTEN mRNA to mi R-135 b, mi R-125 b and Snail mRNA levels in the three endometrium tissues by RT-PCR. Results The levels of TTF-1 and PTEN mRNA in endometrial cancer tissue were both significantly lower than the other two, and were the highest in normal endometrium (P<0.05) .The expressions of TTF-1 and PTEN were no relationship to menopause, adenocarcinoma or squamous cell carcinoma (P >0.05) ; while they were lower as FIGO classes, myometrial invasion and pelvic lymph node metastasis were increasing (P <0.05) .The level of mi R-135 b mRNA in endometrial cancer tissue was significantly higher, while mi R-125 b and Snail mRNA were lower than the other two, mi R-135 b mRNA level in normal endometrium was the lowest, mi R-125 b and Snail mRNA was the highest (P<0.05) .The TTF-1 and PTEN mRNA expressions were positively ralted to mi R-135 b mRNA level, while negatively related to mi R-125 b and Snail mRNA.The diagnosed sensitivity of TTF-1 mRNA for endometrial cancer was 86.5%, specificity84.2%, accuracy 0.823, 95% CI=0.7620.921, P=0.012 by ROC model;while they were 85.3%, 83.6%, 0.842, 95% CI=0.7850.936, P=0.010 of PTEN mRNA correspondingly. Conclusion TTF-1 and PTEN genes can be the molecular markers for early diagnosis of endometrial cancer, are related to clinical features, and may influence tumor by regulating tumor cell proliferation activity.
-
Key words:
- Endometrial cancer /
- Thyroid transcription factor-1 /
- Phosphatase and tensin homolog /
- miR-135b /
- miR-125b /
- Snail
-
[1]王丽琴.子宫内膜癌临床诊治的研究进展[J].中国肿瘤临床与康复, 2012, 19 (5) :472-474. [2]燕鑫, 高雨农, 蒋国庆, 等.临床Ⅰ期子宫内膜癌的手术切除范围及预后影响因素分析[J].中华肿瘤杂志, 2009, 31 (5) :208-212. [3]张丹, 李燕东, 翟林, 等.子宫内膜癌与子宫内膜增生过长病变超声与病理对比分析[J].中华医学超声杂志 (电子版) , 2012, 9 (11) :944-949. [4]张彦兵, 王妍华, 郭亚焕, 等.mi R-135b促进肝癌细胞侵袭和转移[J].细胞与分子免疫学杂志, 2015, 31 (10) :1316-1321. [5]智慧, 朱伟, 王同杉, 等.mi R-125b靶向抑制BCL2、MCL1表达对胃癌SGC7901/VCR细胞多药耐药性的影响[J].南京医科大学学报 (自然科学版) , 2011, 31 (6) :777-782. [6]李娟, 涂媛, 蒋莉莉, 等.Snail和Claudin-3在非小细胞肺癌中的表达及意义[J].中国肺癌杂志, 2012, 15 (10) :583-590. [7] 张晓明, 梁英, 董颖, 等.子宫内膜癌中p-AKT与PTEN、P53、HER-2表达的相关性及意义[J].北京大学学报 (医学版) , 2012, 44 (1) :135-141. [8]李笑, 万里燕, 申洪, 等.血清甲状腺转录因子-1蛋白的变化特点及在肺癌诊断中的意义分析[J].南方医科大学学报, 2011, 31 (9) :1592-1596. [9]钱萍, 高宝莲.卵巢及子宫透明细胞癌、子宫内膜样癌中Napsin A、TTF-1、PAX8及CA125的表达及意义[J].临床与实验病理学杂志, 2017, 33 (2) :192-194. [10]甘露, 许嵩.PTEN和P53蛋白与子宫内膜癌发生发展的相关性研究[J].临床和实验医学杂志, 2016, 15 (21) :2114-2117. [11]岑慧, 柯珮琪, 王莉, 等.PTEN、P27基因甲基化及蛋白表达与子宫内膜癌发生发展的关系[J].实用妇产科杂志, 2012, 28 (1) :28-31. [12]张彤, 沈丹华, 陈云新, 等.PTEN、PAX-2和β-catenin在Ⅰ型子宫内膜癌及其癌前病变中的表达及意义[J].现代妇产科进展, 2014, 23 (2) :85-88. [13] [13]HSU D S, ACHARYA C R, BALAKUMARAN B S, et al.Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer[J].Proc Natl Acad Sci USA, 2009, 106 (13) :5312-5317. [14] [14]YE J, FINDEIS-HOSEY J J, YANG Q, et al.Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung[J].Appl Immunohistochem Mol Morphol, 2011, 19 (4) :313-317. [15]何惠嫦, 黄瑾, 高海洋, 等.EMP2、TTF-1在子宫内膜增生恶变中的表达及意义[J].广东医学院学报, 2016, 34 (3) :268-271. [16] [16]MATIAS-GUIU X, PRAT J.Molecular pathology of endometrial carcinoma[J].Histopathol, 2013, 62 (1) :111-123. [17]乐珍, 沈君菁, 黄启涛, 等.mi R-135b通过靶向FOXO1促进子宫内膜癌细胞的增殖优先出版[J].国外医学医学地理分册, 2016, 36 (5) :675-680. [18] [18]SHI XB XUE L MA AH et al.mi R-125b promotes growth of prostate cancer xenograft tumor throught argeting proapoptotic genes[J].Prostate, 2011, 71 (5) :538-549. [19]冯振中, 陈嘉薇, 甘怀勇, 等.Ⅰ型子宫内膜癌组织中HIF-1α、Snail与E-cadherin的表达及临床意义[J].中国组织化学与细胞化学杂志, 2011, 20 (5) :476-480.
点击查看大图
计量
- 文章访问数: 2281
- HTML全文浏览量: 808
- PDF下载量: 77
- 被引次数: 0