Abstract B093: Upregulated and downregulated microRNA-signatures in thyroid cancer health disparities

Abstract

Abstract Filipino Americans (FA) are known to have a higher incidence, recurrence, and mortality of thyroid cancer (TC) than other Asians Americans or European Americans (EA). Understanding the molecular mechanisms that underpin the genetic defect in metabolism and their impact on thyroid cancer oncogenesis in FA are critical for addressing the health disparity. Mechanisms that link genetic defects and lifestyle factors to thyroid cancer progression have not been defined. Lifestyle and genetic variations among FA lead them to a higher risk of metabolic diseases but no study showed to elucidate the mechanism of thyroid health disparities cancer so far. Recent studies clearly demonstrate that miRNA plays an important role in carcinogenesis via targeting both oncogene and tumor suppressor gene and lifestyle changes may potentially alter miRNA signatures. Therefore, we hypothesize that miRNA expression contributes to tumor grade, prognosis, and thyroid cancer health disparities. We examined miRNA expression profiles in FA vs. EA. We analyzed miRNA-sequence (miRNA-seq) by next-generation sequencing (NGS). The pathways linked to miRNAs were analyzed by ingenuity pathway analysis (IPA) software. Correlations between disease staging to miRNA upregulation and downregulation were elucidated. Both upregulated and downregulated miRNAs were validated by quantitative real-time PCR (qPCR) using miRNA extracted from paraffin-embedded thyroid tissues. We found hundreds of upregulated and downregulated miRNA and piRNA from this study. We chose 10 miRNA down-regulated, and 10 up-regulated miRNA FA compared to EA TC patients (p<0.05). Quantitative PCR (qPCR) was done to confirm our NGS data. Differential miRNA expressions between FA vs. EA patient tumor tissues were observed with advanced staging. Evolutionarily conserved miRNA clusters, which are known to initiate malignancy, were shown to be upregulated in FATC vs. EATC. While those miRNAs are known to regulate pathways involved in cancer invasion and metastasis, they were shown to be down-regulated in FATC patients vs. EATC. The significantly top ten down-regulated/upregulated miRNA-signature suggests that it can be a diagnostic, prognostic, and predictive biomarker in TC health disparities. Citation Format: Ryan Davis, Yan C Wongworawat, Mia C Perez, Krystal Santiago, Saurav Roy, Charles Wang, Alfred A Simental, Salma Khan. Upregulated and downregulated microRNA-signatures in thyroid cancer health disparities [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B093.