Abstract 1464: Identification of metastasis-associated microRNAs in oral squamous cell carcinoma using high-throughput sequencing

MicroRNAs are small noncoding RNAs involved in the initiation and progression of human cancers. Squamous cell carcinoma of the head and neck is among the leading cancers in the world, whereas suitable screening markers or personalized therapy are currently unavailable. MicroRNAs are being tackled as biomarkers with potential to improve outcomes of this disease. The presence of cervical lymph node metastases in head and neck squamous cell carcinoma is currently its strongest prognostic factor and, thus, markers associated with this phenotype are of great interest for the clinical setting. In this study small RNA libraries from 18 oral squamous cell carcinomas were sequenced for the quantification of known microRNAs possibly linked with cervical lymph node metastases. Small RNA populations are especially suitable to analysis using high throughput sequencing technologies since multiple samples can be completely sequenced in a single instrument run. Patients were smokers and heavy drinkers and tumors were grouped according to the presence (N+) or absence (N0) of cervical lymph node metastases at the time of diagnosis. Analysis of the resulting sequences identified 984 distinct mature microRNAs mapping to miRBase (v.19). We observed heterogeneity in regard to microRNA expression among samples from the same group, indicating that microRNA expression patterns associated with cervical metastases in oral cancer is not readily established. For instance, miR-21 and miR-205 were highly expressed throughout samples, in agreement with their role in epithelial cell biology, but disagreeing with studies associating both molecules with cancer invasion. MiR-184, previously detected in high levels in metastatic oral cancer, was detected at low levels at all instances. On the other hand, miR-133a, previously described as a repressor of tumor growth and metastasis, and miR-31, presenting an ability to inhibit several steps in the metastatic process, were both found consistently over-expressed in N0 samples. Abnormal expression of microRNAs is emerging as an important biomarker in cancer and high-throughput sequencing is becoming the technology of choice for the identification and quantification of these molecules. Despite the great potential, we demonstrate that microRNA gene expression varied greatly among patients and across studies. Genetic heterogeneity is a characteristic of head and neck squamous cell carcinomas, impairing consistency in biomarker discovery. We were able