Abstract 4056: MicroRNA-21 and −26a are novel markers to predict the sensitivity to chemotherapy in esophageal squamous cell carcinoma
Authors: Kurashige Junji , Iwatsuki Masaaki , Hiyoshi Yukiharu , Kamohara Hidenobu , Kinoshita Koichi , Saito Seiya , Sato Nobutaka , Karashima Ryuichi , Hirashima Kotaro , Watanabe Masayuki , Baba Hideo 
Published: February 2011

Backgrounds : Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to be cured among gastrointestinal tract cancers. Recently, the effect of neoadjuvant or induction chemotherapy followed by definitive local treatment for advanced ESCC has received much attention through some clinical trials. However, biomarkers which can predict the effect of chemotherapy have not yet been identified. MicroRNA (mir) is a recently discovered class of small non-coding RNAs that can regulate gene expression, and recent researches have demonstrated that changes in expression of some mirs might affect drug resistance. However, there are few reports which identified mirs related to drug resistance to ESCC, using pretreatment biopsy samples.

Objective: In order to identify the mirs which can be biomarkers to predict chemosensitivity inESCC, correlation between the expression status of mirs in biopsy samples and the treatment effects has been investigated.

Patients and methods: Forty patients with node-positive ESCC were eligible for this study from June 2008 to October 2009. Induction chemotherapy using Docetaxel/CDDP/5-FU (DCF) regimen (Docetaxel 60 mg/m2 on day1, 5-FU 350 mg/m2 and cisplatin 6 mg/m2 on day1-5) were given every 3 weeks for 2 courses. Tumor response to chemotherapy was evaluated by 18-F-fluorodeoxyglucose positron emission tomography(FDG-PET) before and after the chemotherapy, and decrease rate of standardized uptake value (SUV) of primary tumors during the chemotherapy has been calculated ((SUVpre - SUV post)/SUVpre X 100 (%)). When the decrease rate was more than%, the treatment was considered to be effective. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) biopsy samples which were collected by upper gastrointestinal endoscopy. We analyzed the expression status of 28 mature mirs, which have been reported to be increased or decreased in ESCC samples or cell lines compared to normal epithelium, by Real-time quantitative RT-PCR.

Results: At first, we have confirmed that expression status of mirs was preserved between FFPE biopsy samples and fresh snap tissues from patients who underwent surgery without any treatments. Among 40 patients treated with induction chemotherapy, there were 22 responders and 18 non-responders. Although 26 out of 28 mirs demonstrated similar expression profiles between responders and non-responders, mir-21and mir-26a were significantly overexpressed in FFPE biopsy samples from non-responders in compared with those from responders (P&lt;0.05). Moreover, pathologic examination of surgically resected specimens revealed that expression of mir-21 and nir-26a was significantly correlated with histopathologic responsiveness.

Conclusions: Expressions of mir-21 and mir-26a in the pretreatment biopsy specimens can be biomarkers to predict response to DCF in patients with ESCC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4056.