MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of multimodality therapy response.

ABSTRACT

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post-therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194 and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194 and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.