The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer.
The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer.
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DOI：
10.1371/journal.pone.0046684
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Takahashi M;Cuatrecasas M;Balaguer F;Hur K;Toiyama Y;Castells A;Boland CR;Goel A
在结直肠癌（CRC）患者中开发稳健的预后和/或预测生物标志物对于推进这种疾病的治疗策略至关重要。我们的目的是确定某些miRNA的表达状态是否可能对接受常规细胞毒性化疗的CRC患者具有预后/预测价值。我们研究了273例接受5-氟尿嘧啶为基础的辅助化疗的II/III期患者和接受5-氟尿嘧啶和奥沙利铂为基础的化疗的IV期患者的CRC标本。在筛选组（n = 44）中，通过多重定量RT-PCR成功定量了21种候选miRNA中的13种。 在包括整个患者队列的验证集中，通过定量RT-PCR评估miR-148 a表达状态，并通过亚硫酸氢盐焦磷酸测序定量其启动子甲基化。最后，我们分析了miR-148 a表达与患者生存率之间的关系。在所研究的候选miRNAs中，miR-148 a的表达在晚期CRC组织中最显著下调。在III期和IV期CRC中，低miR-148 a表达与显著较短的无病生存期（DFS）、较差的治疗反应和较差的总生存期（OS）相关。此外，miR-148 a甲基化状态与其表达呈负相关，并与IV期CRC的生存率较差相关。在多变量分析中，miR-148 a表达是晚期CRC患者的独立预后/预测生物标志物（III期DFS，低表达vs.高表达，HR 2.11; IV期OS，HR 1.93）。miR-148 a状态在用常规化疗治疗的晚期CRC患者中具有预后/预测价值，这在改善这种恶性肿瘤的治疗策略和个性化管理方面具有重要的临床意义。
Development of robust prognostic and/or predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of certain miRNAs might have prognostic/predictive value in CRC patients treated with conventional cytotoxic chemotherapies. We studied a cohort of 273 CRC specimens from stage II/III patients treated with 5-fluorouracil-based adjuvant chemotherapy and stage IV patients subjected to 5-fluorouracil and oxaliplatin-based chemotherapy. In a screening set (n = 44), 13 of 21 candidate miRNAs were successfully quantified by multiplex quantitative RT-PCR. In the validation set comprising of the entire patient cohort, miR-148a expression status was assessed by quantitative RT-PCR, and its promoter methylation was quantified by bisulfite pyrosequencing. Lastly, we analyzed the associations between miR-148a expression and patient survival. Among the candidate miRNAs studied, miR-148a expression was most significantly down-regulated in advanced CRC tissues. In stage III and IV CRC, low miR-148a expression was associated with significantly shorter disease free-survival (DFS), a worse therapeutic response, and poor overall survival (OS). Furthermore, miR-148a methylation status correlated inversely with its expression, and was associated with worse survival in stage IV CRC. In multivariate analysis, miR-148a expression was an independent prognostic/predictive biomarker for advanced CRC patients (DFS in stage III, low vs. high expression, HR 2.11; OS in stage IV, HR 1.93). MiR-148a status has a prognostic/predictive value in advanced CRC patients treated with conventional chemotherapy, which has important clinical implications in improving therapeutic strategies and personalized management of this malignancy.
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影响因子：
4.4
作者：
Jang JS;Simon VA;Feddersen RM;Rakhshan F;Schultz DA;Zschunke MA;Lingle WL;Kolbert CP;Jen J
通讯作者：
Jen J
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
29.4
作者：
Jover R;Nguyen TP;Pérez-Carbonell L;Zapater P;Payá A;Alenda C;Rojas E;Cubiella J;Balaguer F;Morillas JD;Clofent J;Bujanda L;Reñé JM;Bessa X;Xicola RM;Nicolás-Pérez D;Castells A;Andreu M;Llor X;Boland CR;Goel A
通讯作者：
Goel A
影响因子：
4.8
作者：
Fujita, Yasunori;Kojima, Keitaro;Ito, Masafumi
通讯作者：
Ito, Masafumi
影响因子：
7.3
作者：
Lehmann, U.;Hasemeier, B.;Kreipe, H.
通讯作者：
Kreipe, H.