Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab.
Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab.
复制标题
DOI：
10.1371/journal.pone.0109430
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Johansen JS
中科院分区：
文献类型：
--
作者：
Boisen MK;Dehlendorff C;Linnemann D;Nielsen BS;Larsen JS;Osterlind K;Nielsen SE;Tarpgaard LS;Qvortrup C;Pfeiffer P;Holländer NH;Keldsen N;Hansen TF;Jensen BB;Høgdall EV;Jensen BV;Johansen JS
我们验证了癌症组织中microRNAs （miRNAs）的表达可以预测转移性结直肠癌（mCRC）患者贝伐单抗加卡培他滨和奥沙利铂（CAPEOX）的有效性的假设。采用一线CAPEOX和贝伐单抗（CAPEOXBEV）治疗的mCRC患者：筛选（n = 212）和验证（n = 121）队列，或单独使用CAPEOX：对照队列（n = 127），回顾性确定并收集档案原发肿瘤样本。使用聚合酶链反应（PCR）阵列分析筛选队列中754个mirna的表达，表达水平与疾病进展时间（TTP）和总生存期（OS）相关。使用定制PCR阵列分析筛选研究中所有三个队列中的重要mirna。对选定的mirna进行原位杂交（ISH）。在筛选研究中，26种mirna在多变量分析中与结果显著相关。选择22个mirna进行进一步研究。在CAPEOXBEV队列中，较高的miR-664-3p表达和较低的miR-455-5p表达预示着预后的改善，并显示出与贝伐单抗有效性的显著相互作用。对OS的影响最大。这两种mirna在基质细胞中均有高表达。无论贝伐单抗治疗如何，miR-196b-5p和miR-592的高表达预测了预后的改善，在所有三个队列中均具有相似的效果估计。我们已经确定了贝伐单抗有效性的潜在预测miRNAs，以及可能与mCRC患者化疗有效性或预后相关的其他miRNAs。我们的发现需要在更大的队列中进一步验证，最好是在完成的随机试验中。
We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs. In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.
登录
查看更多内容
DOI：
10.1111/j.1749-6632.2010.05822.x
发表时间：
2010-01-01
期刊：
TOWARD PERSONALIZED MEDICINE FOR CANCER
影响因子：
--
作者：
Nana-Sinkam, S. Patrick;Fabbri, Muller;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
3.9
作者：
Mazeh H;Mizrahi I;Ilyayev N;Halle D;Brücher B;Bilchik A;Protic M;Daumer M;Stojadinovic A;Itzhak A;Nissan A
通讯作者：
Nissan A
影响因子：
1.9
作者：
Mosakhani, Neda;Lahti, Leo;Sarhadi, Virinder Kaur
通讯作者：
Sarhadi, Virinder Kaur
影响因子：
45.3
作者：
Giantonio, Bruce J.;Catalano, Paul J.;Benson, Al B., III
通讯作者：
Benson, Al B., III
影响因子：
45.3
作者：
Kopetz, Scott;Chang, George J.;McWilliams, Robert R.
通讯作者：
McWilliams, Robert R.