Background:

MicroRNAs (miRNAs) are a class of small non-coding RNAs that inhibit gene expression by binding to 3` untranslated regions of mRNAs and inhibiting their translation. MiRNAs crucially affect cellular processes such as development, proliferation, differentiation and apoptosis, which are deregulated in cancer. MiR-503 is located at Xq26.3 and belongs to an extended miR-16 family of miRNAs. MiR-503 is down-regulated in several types of cancer, including oral, hepatocellular, gastric, and endometrial cancer, suggesting that it plays a tumour-suppressor role in carcinogenesis. In contrast, other recent reports have demonstrated up-regulation of miR-503 in adrenocortical carcinoma, parathyroid and retinoblastoma, compared with adjacent normal tissue. These results suggest that miR-503 shows tissue- or disease-specific expression patterns. However, miR-503 expression patterns in esophageal cancer (EC) and normal esophageal tissue have not been compared and the correlation of miR-503 expression with the clinical features of EC has not been studied.

Materials and Methods:

A total of 61 formalin-fixed paraffin-embedded (FFPE) tissue samples including 49 EC tissues and 12 adjacent normal esophageal tissues who underwent surgical resection at Mie University Hospital were collected from 2003 to 2013. Tagman qRT-PCR assay was performed to quantify the miR-503 expression in EC and adjacent normal tissues. We analyzed the association between miR-503 expression and clinico-pathological factors in patients with EC.

Results:

The median age of the patients was 66.2 years (41 - 90). The median follow up time was 24.6 months (3.8 - 80.0). There were 3 patients with stage 0, 16 with stage I, 12 with stage II, 11 with stage III, 3 with stage IVa and 4 with stage IVb by using the criteria of the Japanese Classification of Esophageal Cancer, 10th edition. Forty-four patients had esophageal squamous cell carcinoma (ESCC), five patients had esophageal adenocarcinoma (EAD). MiR-503 was remarkably up-regulated in EC tissues compared to adjacent normal tissue. High miR-503 expression in EC was significantly associated with male sex and large tumor size. Kaplan-Meier analysis showed that patients with high miR-503 expression had significantly poorer disease free and overall survival than those with low expression. Furthermore, high miR-503 expression was an independent predictor for prognosis in EC patients according to multivariate analysis.

Conclusions:

The results of this study provide novel evidence for associations between miR-503 expression and progression, early recurrence, and poor prognosis in EC, suggesting that it acts as an oncomiR in this type of cancer. MiR-503 may thus be a promising predictive marker for prognosis after surgery in patients with EC.

Citation Format: Koichiro Mori, Yuji Toiyama, Shozo Ide, Tomofumi Noguchi, Hiroki Imaoka, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Yasuhiro Inoue, Koji Tanaka, Yasuhiko Mohri, Tsutomu Nobori, Masato Kusunoki. MicroRNA-503 promotes tumor progression and acts as a novel biomarker for prognosis in esophageal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3401. doi:10.1158/1538-7445.AM2015-3401