Department of Oncology, Vejle Hospital, Kabbeltoft, Denmark.
BMC Cancer. 2012 Mar 8;12:83. doi: 10.1186/1471-2407-12-83.
MicroRNA-126 is the only microRNA (miRNA) known to be endothelial cell-specific influencing angiogenesis in several ways. The aim of the present study was to analyse the possible predictive value of miRNA-126 in relation to first line capecitabine and oxaliplatin (XELOX) in patients with metastatic colorectal cancer (mCRC).
The study included 89 patients with mCRC. In situ hybridization (ISH) was performed to detect miRNA-126 in formalin-fixed paraffin embedded tissue from primary tumours. The expression of miRNA-126, area per image (μm(2)), was measured using image analysis. Clinical response was evaluated according to RECIST. Progression free survival (PFS) was compared using the Kaplan-Meier method and the log rank test. Tumours were classified as low or high miRNA-126 expressing tumours using the median value from the patients with response as cut-off.
The median miRNA-126 expression level was significantly higher in patients responding to XELOX, 3629 μm(2) (95% CI, 2566-4846), compared to the patients not responding, 1670 μm(2) (95% CI, 1436-2041), p < 0.0001. The positive predictive value was 90%, and the negative predictive value was 71%. The median PFS of patients with high expressing tumours was 11.5 months (95% CI, 9.0-12.7 months) compared to 6.0 months (95% CI, 4.8-6.9 months) for patients with low expressing tumours, p < 0.0001.
Angiogenesis quantified by ISH of miRNA-126 was related to response to first line XELOX in patients with mCRC, translating to a significant difference in PFS. The predictive value of miRNA-126 remains to be further elucidated in prospective studies.
miRNA-126 是唯一已知的内皮细胞特异性 miRNA,可通过多种方式影响血管生成。本研究旨在分析 miRNA-126 与转移性结直肠癌(mCRC)一线卡培他滨和奥沙利铂(XELOX)的可能预测价值。
该研究纳入了 89 例 mCRC 患者。采用原位杂交(ISH)检测原发肿瘤福尔马林固定石蜡包埋组织中 miRNA-126 的表达。使用图像分析测量 miRNA-126 的表达量(每图像面积,μm2)。根据 RECIST 评估临床反应。采用 Kaplan-Meier 法和对数秩检验比较无进展生存期(PFS)。使用有反应患者的中位数作为截断值,将肿瘤分为 miRNA-126 低表达和高表达肿瘤。
XELOX 治疗有效患者的 miRNA-126 中位表达水平明显高于无反应患者,分别为 3629 μm2(95%CI,2566-4846)和 1670 μm2(95%CI,1436-2041),p<0.0001。阳性预测值为 90%,阴性预测值为 71%。高表达肿瘤患者的中位 PFS 为 11.5 个月(95%CI,9.0-12.7 个月),低表达肿瘤患者为 6.0 个月(95%CI,4.8-6.9 个月),p<0.0001。
通过 ISH 定量测定的 miRNA-126 血管生成与 mCRC 患者一线 XELOX 治疗的反应相关,进而导致 PFS 显著差异。miRNA-126 的预测价值仍需在前瞻性研究中进一步阐明。