Prognostic significance of differentially expressed miRNAs in esophageal cancer.

Prognostic significance of differentially expressed miRNAs in esophageal cancer.
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DOI:
10.1002/ijc.25330
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发表时间:
2011-01-01
影响因子:
6.4
通讯作者:
Xu, Xiao-Chun
Xu, Xiao-Chun
中科院分区:
医学1区
文献类型:
--
作者:
Hu, Yuxin;Correa, Arlene M.;Hoque, Ashraful;Guan, Baoxiang;Ye, Fei;Huang, Jie;Swisher, Stephen G.;Wu, Tsung Teh;Ajani, Jaffer A.;Xu, Xiao-Chun

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已经发现microRNA (miRNA)表达改变可促进癌变,但对其在食管癌中的作用知之甚少。在本研究中,我们选择了10个mirna,分别用Northern blotting和原位杂交技术分析了它们在10个食管癌细胞系和158个组织标本中的表达。我们发现,Let-7g、miR-21和miR-195p在所有10个细胞系中都有表达,miR-9和miR-20a在任何细胞系中都不表达,miR-16-2、miR-30e、miR-34a、miR-126和miR-200a在一些细胞系中表达,而在其他细胞系中不表达。此外,短暂转染miR-34a可抑制c-Met和cyclin D1的表达和食管癌细胞的增殖,而miR-16-2可抑制RAR-β2的表达,增加肿瘤细胞的增殖。此外,我们发现miR-126的表达与肿瘤细胞去分化和淋巴结转移有关,miR-16-2与淋巴结转移有关,miR-195p与食管腺癌患者较高的病理疾病分期有关。Kaplan-Meier分析显示,在所有食管癌患者中,miR-16-2和miR-30e的表达与较短的总生存期和无病生存期相关。此外,miR-16-2、miR-30e和miR-200a的表达与食管腺癌患者较短的总生存期和无病生存期相关;然而,miR-16-2、miR-30e和miR-200a的表达与鳞状细胞癌患者的总生存率或无病生存率无关。我们的数据表明,进一步评估miR-30e和miR-16-2作为食管癌患者预后的生物标志物是有必要的。此外,miR-34a在食管癌中的作用也有待进一步研究。
Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21, and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126, and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-β2 expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell de-differentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e, and miR-200a expression were associated with shorter overall and disease-free survival in esophageal adenocarcinoma patients; however, miR-16-2, miR-30e, and miR-200a expression was not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.
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