MicroRNA expression profiling of esophageal cancer before and after induction chemoradiotherapy

Abstract

Background: 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.

Methods: 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).

Results: 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).

Conclusions: 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.