Division of Thoracic Surgery, St. Joseph's Health Centre, University Health Network, Toronto, Ontario, Canada.
Ann Thorac Surg. 2012 Oct;94(4):1094-102; discussion 1102-3. doi: 10.1016/j.athoracsur.2012.04.145. Epub 2012 Aug 29.
The prognosis for esophageal cancer is poor but may be improved by neoadjuvant therapy. A complete pathologic response (pCR) is associated with improved survival. We conducted a study to profile the expression of microRNAs (miRNAs) in esophageal cancer before and after induction therapy. Our aims were to identify those miRNAs that are differentially regulated after induction therapy and attempt to describe a miRNA pattern that could predict pCR.
Total RNA was extracted from pretreatment and posttreatment specimens from 25 patients who underwent trimodal therapy using concurrent irinotecan/cisplatin and radiotherapy followed by surgical treatment. miRNAs were labeled and hybridized to the Illumina miRNA BeadChip microarray (Illumina, Inc, San Diego, CA). Expression data was quantified using BeadStudio software (Illumina), using a cutoff for significant gene differences of p less than 0.05 with a 2-fold difference in expression. Survival analysis was performed using SPSS, version 18 (SPSS, Inc, Chicago, IL).
Using pretreatment biopsy specimens, 71 miRNAs were significantly different between pCR and non-pCR groups. Of these, 5 miRNAs were greater than 2-fold differentially regulated, including miR-296, recently shown to be of prognostic significance in esophageal carcinoma. After induction therapy, 568 miRNAs were found to be significantly upregulated or downregulated, 111 of which had a 2-fold difference. Patients with high levels of miR-135b or miR-145 in the posttreatment biopsy specimens had significantly shorter median disease-free survival (DFS) than did those with low levels (11.5 versus 5.1 months; p=0.04; 11.5 versus 2.8 months; p=0.03).
miRNA expression profiling of pretreatment biopsy specimens revealed 5 miRNAs differentially expressed in patients with pCR compared with patients without pCR. We have also identified 111 miRNAs significantly upregulated or downregulated after induction therapy, some of which may be predictive of outcome. Further study of these miRNAs may elucidate a novel understanding of mechanisms of resistance to chemotherapy or radiotherapy.
食管癌的预后较差，但新辅助治疗可能会改善预后。完全病理缓解（pCR）与生存改善相关。我们进行了一项研究，以分析食管癌患者在诱导治疗前后的 microRNA（miRNA）表达谱。我们的目的是确定那些在诱导治疗后差异表达的 miRNA，并尝试描述一种可以预测 pCR 的 miRNA 模式。
从 25 例接受三联疗法（同时使用伊立替康和顺铂和放疗）治疗后接受手术治疗的患者的预处理和治疗后标本中提取总 RNA。使用 Illumina miRNA BeadChip 微阵列（Illumina，Inc.，圣地亚哥，CA）对 miRNA 进行标记和杂交。使用 BeadStudio 软件（Illumina）对表达数据进行定量，使用 p 值小于 0.05 和表达差异倍数为 2 的基因差异的截止值来确定显著基因差异。使用 SPSS 版本 18（SPSS，Inc.，芝加哥，IL）进行生存分析。
使用预处理活检标本，在 pCR 和非 pCR 组之间，71 个 miRNA 有显著差异。其中，5 个 miRNA 的表达差异倍数大于 2 倍，包括 miR-296，最近被证明在食管癌中有预后意义。在诱导治疗后，发现 568 个 miRNA 显著上调或下调，其中 111 个差异倍数为 2 倍。在治疗后活检标本中高水平的 miR-135b 或 miR-145 的患者中位无疾病生存（DFS）显著短于低水平的患者（11.5 个月对 5.1 个月；p=0.04；11.5 个月对 2.8 个月；p=0.03）。
预处理活检标本的 miRNA 表达谱分析显示，在 pCR 患者与无 pCR 患者之间，有 5 个 miRNA 差异表达。我们还鉴定了 111 个在诱导治疗后显著上调或下调的 miRNA，其中一些可能与预后相关。对这些 miRNA 的进一步研究可能会阐明对化疗或放疗耐药机制的新认识。
