Prognostic significance of miR-215 in colon cancer.
Prognostic significance of miR-215 in colon cancer.
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DOI：
10.1016/j.clcc.2011.06.002
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发表时间：
2011-12
影响因子：
3.4
通讯作者：
Ju J
中科院分区：
文献类型：
--
作者：
Karaayvaz M;Pal T;Song B;Zhang C;Georgakopoulos P;Mehmood S;Burke S;Shroyer K;Ju J
研究了 miR-215 作为结肠癌潜在生物标志物的临床效用。通过实时 qRT-PCR 对 34 配对的正常和肿瘤样本中的 miR-215 水平进行定量。结肠肿瘤中 miR-215 的表达水平降低，并且与患者生存相关。因此，miR-215是结肠癌潜在的预后生物标志物。我们之前已经证明，miR-215 抑制了结肠癌中胸苷酸合酶（TS）、二氢叶酸还原酶和无齿蛋白同源物（DTL）等关键靶标的表达。 miR-215 是一种候选肿瘤抑制因子，因为它通过靶向 DTL 上调 p53 和 p21。然而，高水平的 miR-215 由于细胞周期停滞而产生化疗耐药性，并通过抑制 DTL 减少细胞增殖。在这项研究中，进一步研究了 miR-215 作为结肠癌患者潜在预后生物标志物的临床意义。使用基于 Trizol 的方法从 34 对正常和结肠（II 期和 III 期）肿瘤样本中提取总 RNA。使用定量实时聚合酶链反应 (qRT-PCR) 表达分析对 miR-215 和密切相关的 miR-192 的水平进行定量。通过实时 qRT-PCR 和免疫组织化学对 DTL mRNA 和蛋白的表达进行定量。与正常组织相比，结肠肿瘤中 miR-192 (P = .0008) 和 miR-215 (P < .0001) 的表达水平显着降低。 DTL 显着过度表达，并且与 miR-215 呈负相关，进一步表明 miR-215 介导的 DTL 抑制具有体内生理相关性。通过 Cox 回归进行的 Kaplan-Meier 生存分析显示，高水平的 miR-215 表达（风险比，3.516；95% 置信区间，1.007–12.28，P = .025）与较差患者的总生存期密切相关。此外，在结肠癌组织中检测到miR-215靶蛋白DTL表达升高，而在正常组织中不表达。 miR-215 作为 II 期和 III 期结肠癌的预后生物标志物具有独特的潜力。
The clinical utility of miR-215 as a potential biomarker in colon cancer was investigated. The levels of miR-215 were quantified by real-time qRT-PCR in 34 paired normal and tumor specimens. The expression levels of miR-215 were decreased in colon tumors, and were associated with patient survival. Thus, miR-215 is a potential prognostic biomarker in colon cancer. We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients. Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry. The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007–12.28, P = .025) are closely associated with poor patient’s overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues. miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
12.4
作者：
Ghodgaonkar, M. M.;Shah, R. G.;Shah, G. M.
通讯作者：
Shah, G. M.
影响因子：
4.3
作者：
Banks, Damon;Wu, Min;Zhang, Hui
通讯作者：
Zhang, Hui
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1158/1078-0432.ccr-10-0052
发表时间：
2010-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
McLornan DP;Barrett HL;Cummins R;McDermott U;McDowell C;Conlon SJ;Coyle VM;Van Schaeybroeck S;Wilson R;Kay EW;Longley DB;Johnston PG
通讯作者：
Johnston PG