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.
Highlights
Thyroid cancer (TC) is the most common type of endocrine malignancy, and the incidence of TC has increased in the last few decades [1,2,3,4]
This study consists of de-identified discarded tissue samples from both Filipino American (1st generation Filipinos who have resided in the USA for the last 20 years) and European American (Europeans who have been residing in the USA) patients with thyroid cancer, aged 18–80 years, and from both sexes with adequate clinical information and paraffin blocks for immunohistochemistry (IHC)
Our sequencing data showed that the vast majority of miRNAs are downregulated and unchanged, whereas only a few are upregulated, in Filipino Americans when compared to European Americans as positive controls (Figure 2)
Summary
Thyroid cancer (TC) is the most common type of endocrine malignancy, and the incidence of TC has increased in the last few decades [1,2,3,4]. Cancer Institute recognizes Asians as one of the most at-risk ethnicities for TC [9]. Filipinos have a notably higher risk of developing TC compared to other races/ethnicities [10,11,12]. Data showed that Filipino women have a higher incidence rate with a peak age range from 45–54. In Filipino American women, a higher rate of recurrence was reported, especially in premenopausal women. It has been found that the recurrence rate is higher in Filipino Americans [7,10,12,15,16]
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