Differential Expression of Non-Coding RNA Signatures in Thyroid Cancer between Two Ethnic Groups.

ABSTRACT

Filipino Americans show higher thyroid cancer recurrence rates compared to European Americans. Although they are likely to die of this malignancy, the molecular mechanism has not yet been determined. Recent studies demonstrated that small non-coding RNAs could be utilized to assess thyroid cancer prognosis in tumor models. The goal of this study is to determine whether microRNA (miRNA) signatures are differentially expressed in thyroid cancer in two different ethnic groups. We also determined whether these miRNA signatures are related to cancer staging. This is a retrospective study of archival samples from patients with thyroid cancer (both sexes) in the pathology division from the last ten years at Loma Linda University School of Medicine, California. Deidentified patient demographics were extracted from the patient chart. Discarded formalin-fixed paraffin-embedded tissues were collected post-surgeries. We determined the differential expressions of microRNA in archival samples from Filipino Americans compared to European Americans using the state-of-the-art technique, HiSeq4000. By ingenuity pathway analysis, we determined miRNA targets and the pathways that those targets are involved in. We validated their expressions by real-time quantitative PCR and correlated them with the clinicopathological status in a larger cohort of miRNA samples from both ethnicities. We identified the differentially upregulated/downregulated miRNA clusters in Filipino Americans compared to European Americans. Some of these miRNA clusters are known to target genes that are linked to cancer invasion and metastasis. In univariate analysis, ethnicity and tumor staging were significant factors predicting miR-4633-5p upregulation. When including these factors in a multivariate logistic regression model, ethnicity and tumor staging remained significant independent predictors of miRNA upregulation, whereas the interaction of ethnicity and tumor staging was not significant. In contrast, ethnicity remained an independent predictor of significantly downregulated miR-491-5p and let-7 family. We provide evidence that Filipino Americans showed differentially expressed tumor-tissue-derived microRNA clusters. The functional implications of these miRNAs are under investigation.